A neurosphere-derived factor, cystatin C, supports differentiation of ES cells into neural stem cells.

Although embryonic stem (ES) cells are capable of unlimited proliferation and pluripotent differentiation, effective preparation of neural stem cells from ES cells are not achieved. Here, we have directly generated under the coculture with dissociated primary neurosphere cells in serum-free medium and the same effect was observed when ES cells were cultured with conditioned medium of primary neurosphere culture (CMPNC). ES-neural stem cells (NSCs) could proliferate for more than seven times and differentiate into neurons, astrocytes, and oligodendrocytes in vitro and in vivo. The responsible molecule in CMPNC was confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, which turned out to be cystatin C. Purified cystatin C in place of the CMPNC could generate ES-NSCs efficiently with self-renewal and multidifferentiation potentials. These results reveal the validity of cystatin C for generating NSCs from ES cells.

[Postoperative complete atrioventricular block induced by carbamazepine in a patient with congenital heart disease].

We report here a boy with epilepsy and congenital heart defect, complicated postoperatively by complete atrioventricular (A-V) block caused by an adverse effect of carbamazepine (CBZ). He had been taking CBZ for 7 years to treat complex partial seizures. He also had endocardial cushion defect and first-degree A-V block, and underwent cardiac surgery at the age of 17 years. The postoperative course was unremarkable except transient complete left bundle branch block occuring one day after the surgery. Oral CBZ (400 mg per day) was continued. Five days after the surgery, bradycardia (20 beats per minute) suddenly developed, and electrocardiography (ECG) showed complete A-V block. Pervenous pacing was begun, and the heart rate gradually recovered. CBZ was discontinued on the suspicion that it caused the arrhythmia, although its serum level was estimated to be within the therapeutic range (4 to 5 microg/ml). He underwent pervenous pacing for 12 days. He was discharged 27 days after the surgery, when ECG returned to first-degree A-V block. In this case, the cardiac conduction system was affected by an adverse effect of CBZ, in combination with the preoperative first-degree A-V block and the effects of cardiac surgery, resulting in complete A-V block. Although reports of similar cases are scarce, caution should be made in prescribing CBZ to patients who either have cardiac conduction abnormalities or undergo cardiac surgery.

Multi-institutional study on the correlation between chromosomal abnormalities and epilepsy.

While there is an abundance of literature describing the association of chromosome aberrations with epilepsy, only a few refer to the detailed features of epilepsy. It is important to investigate the associations between specific chromosome abnormalities and features of epilepsy to identify genes involved in epilepsy and treat them more effectively. We investigated the correlation between specific chromosome aberrations and epilepsy by sending questionnaires to the members of Kyoto Multi-institutional Study Group of Pediatric Neurology. Seventy-six patients were collected from 10 institutions. Chromosome abnormalities included: Down syndrome (n = 19); Angelman syndrome (n = 8); Prader-Willi syndrome (n = 4); 4p- syndrome (n = 3); 1q- syndrome (n = 2); 5p- syndrome (n = 2); Miller-Dieker syndrome (n = 2); 18q- syndrome; (n = 2); Klinefelter syndrome; (n = 2); and 32 other individual chromosomal aberrations. Overall, the severity of mental retardation correlated with the severity of epilepsy. We could abstract characteristic features of epilepsy in some syndromes. In Angelman and Prader-Willi syndromes, febrile seizures occurred frequently, the onset of epilepsy was in early childhood and seizure phenotype was multiple. Paroxysmal discharge of the occipital region and diffuse high voltage slow wave on electroencephalography were characteristic in Angelman syndrome. In Down syndrome, West syndrome and focal epilepsy were common and the prognosis of epilepsy in West syndrome with Down syndrome was good. In 4p- syndrome, febrile seizures were often seen, and unilateral or generalized clonic or tonic-clonic status epilepticus were characteristic. For the other chromosomal aberrations investigated here, the patient numbers were too small to abstract common features of epilepsy.

MR imaging with quantitative diffusion mapping of tacrolimus-induced neurotoxicity in organ transplant patients.

Our objective was to investigate brain MR imaging findings and the utility of diffusion-weighted (DW) imaging in organ transplant patients who developed neurologic symptoms during tacrolimus therapy. Brain MR studies, including DW imaging, were prospectively performed in 14 organ transplant patients receiving tacrolimus who developed neurologic complications. In each patient who had abnormalities on the initial MR study, a follow-up MR study was performed 1 month later. Apparent diffusion coefficient (ADC) values on the initial MR study were correlated with reversibility of the lesions. Of the 14 patients, 5 (35.7%) had white matter abnormalities, 1 (7.1%) had putaminal hemorrhage, and 8 (57.1%) had normal findings on initial MR images. Among the 5 patients with white matter abnormalities, 4 patients (80.0%) showed higher than normal ADC values on initial MR images, and all showed complete resolution on follow-up images. The remaining 1 patient (20.0%) showed lower than normal ADC value and showed incomplete resolution with cortical laminar necrosis. Diffusion-weighted imaging may be useful in predicting the outcomes of the lesions of tacrolimus-induced neurotoxicity.

Acute lethal encephalopathy in systemic juvenile rheumatoid arthritis.

Macrophage activation syndrome is the most common cause of death in children with systemic juvenile rheumatoid arthritis. We present a first patient with systemic juvenile rheumatoid arthritis in which acute necrotizing encephalopathy developed as a complication of macrophage activation syndrome but not of Reye's syndrome. The suspected mechanism of this lethal complication is discussed.

Subclinical central pontine myelinolysis following liver transplantation.

Central pontine myelinolysis (CPM) is a demyelinating disorder of unknown origin that almost exclusively affects the central portion of the basis pontis, and is one of the fatal neurological complications after liver transplantation. We describe two children with CPM detected incidentally after liver transplantation. To our knowledge, this is the first report of CPM diagnosed antemortem in children who had undergone liver transplantation. In our patients, there were no clinical manifestations associated with CPM. We conclude that, including silent cases such as our patients, CPM may be more prevalent than previously appreciated following liver transplantation.

Non-progressive viral myelitis in X-linked agammaglobulinemia.

We report a 14-year-old boy with X-linked agammaglobulinemia (XLA) complicated by isolated non-progressive myelitis caused by Coxsackie virus B1. Despite the absence of immunoglobulin supplement and persistence of the virus for the initial 2 years, motor impairment did not show any progression for 3 years. This report shows that the prognosis of central nervous system infection in XLA is not determined by immunoglobulin levels alone, and that it is not always progressive or fatal. The balance between host immunity and the virulence of the causative virus may be involved in the prognosis of meningoencephalitis in XLA.