Pyridoxine-dependent epilepsy usually presents in the neonatal period or even in utero, is refractory to antiepileptic medications, and is treatable with lifelong administration of pyridoxine. The seizures are typically generalized tonic-clonic, although myoclonic seizures or infantile spasms have been described. We report an infant who presented at 5 months of age with a right-sided clonic seizure with fever. Subsequently, she had recurrent right focal or generalized seizures despite sequential treatment with various antiepileptic medications. At 7 months, she was hospitalized with status epilepticus, which was finally controlled with pyridoxine. After she became seizure free, she continued to have a strong left arm preference with mild weakness of the right arm and delayed language skill. Eventually, she outgrew these symptoms. This case illustrates that pyridoxine-dependent epilepsy, although rare, must be included in the differential diagnosis of focal seizures, especially when the seizures are refractory to traditional antiepileptic drugs. ( J Child Neurol 2005;20:696—698).
In Prader–Willi syndrome, the neuropathologic abnormalities causative for central hypotonia or cognitive delay are largely unknown. We report a girl diagnosed with Prader–Willi syndrome in whom cranial MRI showed a diffusely abnormal cerebral gyral folding pattern strongly suggestive of a cortical malformation.
The patient was born to a 27-year-old mother. The pregnancy was normal prior to a cesarean section performed at 35 weeks gestational age because of vaginal bleeding from placenta previa. Apgar scores were 4 at 1 minute and 6 at 5 minutes. The patient appeared flaccid, and her cry was weak. On day one of her life, she developed respiratory distress. She was intubated and treated with surfactant. She was profoundly hypotonic, hypersomnolent, and had difficulty in feeding during her hospital stay. No convulsive movements, prolonged apnea, or abnormal eye or facial movements were observed. On examination, her head circumference at birth was 38 cm (greater than 95th percentile) and her weight was 2.5 kg (50th to 75th percentile). Her anterior and posterior fontanelles were widely open. She had prominent forehead, low set ears, small palpebral fissures, and small …
A good correlation was observed between enhanced lung cancer risk and restriction fragment length polymorphisms (RFLPs) of the P450IA1 gene with the restriction enzyme Msp I. Genotype frequencies of 0.49 for the predominant homozygote, 0.40 for the heterozygote, and 0.11 for the homozygous rare allele were observed in a healthy population. Among lung cancer patients, the frequency of homozygous rare allele of P450IA1 gene was found to be about 3‐fold higher than that among healthy population, and this difference was statistically significant. This is the first report to identify the genetically high risk individuals to lung cancer at the gene level.
Immunoperoxidase staining of frozen sections from surgically removed melanoma lesions showed that anti-human leukocyte antigen (HLA)-A2, A28 monoclonal antibody (mAb) stained keratinocytes, but did not stain melanoma cells in 21% of the 14 primary and 44% of the 9 metastatic lesions tested. The loss of HLA-A2 and/or A28 allospecificities did not affect the staining patterns with mAb recognizing monomorphic determinants of HLA Class I antigens, in terms of percentage of stained melanoma cells and intensity of staining. This finding is not likely to reflect the sensitivity of the immunoperoxidase technique, since cytofluorographic analysis detected no significant difference in the staining pattern by mAb to monomorphic determinants of HLA Class I antigens between a melanoma cell line and an autologous transfectant that had acquired HLA-A2 antigens following gene transfer. The results of the present study imply that the frequency of abnormalities in HLA Class I antigen expression by melanoma cells is higher than that described in the literature, since selective losses of HLA Class I allospecificities are not detected by staining of melanoma cells with mAb to monomorphic determinants of HLA Class I antigens. The latter reagents have been used in most of the published studies to characterize the expression of HLA Class I antigens in melanoma lesions. Furthermore, the present results provide a mechanism for the unexpected resistance to cytotoxic T-cell-mediated lysis and the unexpected poor clinical course of the disease in some patients despite a high expression of HLA Class I antigens as measured by staining of melanoma cells with mAb to monomorphic determinants.
Brain-derived neurotrophic factor (BDNF) is a prototypic neurotrophin that regulates diverse developmental events from the selection of neural progenitors to the terminal dendritic differentiation and connectivity of neurons. We focus here on activity-dependent synaptic regulation by BDNF and its receptor, full length TrkB. BDNF-TrkB signaling is involved in transcription, translation, and trafficking of proteins during various phases of synaptic development and has been implicated in several forms of synaptic plasticity. These functions are carried out by a combination of the three signaling cascades triggered when BDNF binds TrkB: the mitogen-activated protein kinase (MAPK), the phospholipase Cγ (PLC PLCγ), and the phosphatidylinositol 3-kinase (PI3K) pathways. MAPK and PI3K play crucial roles in both translation and/or trafficking of proteins induced by synaptic activity while PLCγ regulates intracellular Ca2+ that can drive transcription via cyclic AMP and a Protein Kinase C. Conversely, the abnormal regulation of BDNF is implicated in various developmental and neurodegenerative diseases that perturb neural development and function. We will discuss the current state of understanding BDNF signaling in the context of synaptic development and plasticity with a focus on the post-synaptic cell and close with the evidence that basic mechanisms of BDNF function still need to be understood in order to effectively treat genetic disruptions of these pathways that cause devastating neurodevelopmental diseases.
