Neurology Copyright (c) 2013 University of Massachusetts Medical School All rights reserved. http://escholarship.umassmed.edu/peds_neurology Recent documents in Neurology en-us Wed, 13 Feb 2013 18:02:28 PST 3600 Dysembryoplastic neuroepithelial tumor located in pericallosal and intraventricular area in a child. Case report http://escholarship.umassmed.edu/peds_neurology/19 http://escholarship.umassmed.edu/peds_neurology/19 Wed, 20 Jun 2012 11:23:08 PDT Dysembryoplastic neuroepithelial tumors (DNETs) are frequently seen in children and young adults with intractable epilepsy, and are typically located in the temporal cortex. Extracortical location of DNET is a very rare occurrence. The authors report on a child with a unique extracortical location of DNET with an extensive involvement to the supracallosal cistern and callosum, septum pellucidum, and lateral ventricle ependyma. The authors discuss the radiological and pathological characteristics of the lesion and reiterate the difficulty in differentiating the histological characteristics of central neurocytoma and DNET in extracortical locations and its significance for further management planning.

]]> Oguz Cataltepe et al. Adolescent Brain Neoplasms Cerebral Ventricle Neoplasms Corpus Callosum Humans Male Neoplasms, Neuroepithelial Teratoma Glial activation links early-life seizures and long-term neurologic dysfunction: evidence using a small molecule inhibitor of proinflammatory cytokine upregulation http://escholarship.umassmed.edu/peds_neurology/18 http://escholarship.umassmed.edu/peds_neurology/18 Wed, 20 Jun 2012 11:23:04 PDT PURPOSE: Early-life seizures increase vulnerability to subsequent neurologic insult. We tested the hypothesis that early-life seizures increase susceptibility to later neurologic injury by causing chronic glial activation. To determine the mechanisms by which glial activation may modulate neurologic injury, we examined both acute changes in proinflammatory cytokines and long-term changes in astrocyte and microglial activation and astrocyte glutamate transporters in a "two-hit" model of kainic acid (KA)-induced seizures.

METHODS: Postnatal day (P) 15 male rats were administered KA or phosphate buffered saline (PBS). On P45 animals either received a second treatment of KA or PBS. On P55, control (PBS-PBS), early-life seizure (KA-PBS), adult seizure (PBS-KA), and "two-hit" (KA-KA) groups were examined for astrocyte and microglial activation, alteration in glutamate transporters, and expression of the glial protein, clusterin.

RESULTS: P15 seizures resulted in an acute increase in hippocampal levels of IL-1beta and S100B, followed by behavioral impairment and long-term increases in GFAP and S100B. Animals in the "two-hit" group showed greater microglial activation, neurologic injury, and susceptibility to seizures compared to the adult seizure group. Glutamate transporters increased following seizures but did not differ between these two groups. Treatment with Minozac, a small molecule inhibitor of proinflammatory cytokine upregulation, following early-life seizures prevented both the long-term increase in activated glia and the associated behavioral impairment.

CONCLUSIONS: These data suggest that glial activation following early-life seizures results in increased susceptibility to seizures in adulthood, in part through priming microglia and enhanced microglial activation. Glial activation may be a novel therapeutic target in pediatric epilepsy.

]]> Kathleen C. Somera-Molina et al. Age Factors Amino Acid Transport System X-AG Animals Astrocytes Blotting, Western Clusterin *Complement Factor H Cytokines Disease Models, Animal Disease Susceptibility Fluorescent Antibody Technique Hippocampus Immunohistochemistry Inflammation Kainic Acid Male Microglia Neuroglia Random Allocation Rats Rats, Sprague-Dawley Seizures Severity of Illness Index Up-Regulation Depressive behavior and selective down-regulation of serotonin receptor expression after early-life seizures: reversal by environmental enrichment http://escholarship.umassmed.edu/peds_neurology/17 http://escholarship.umassmed.edu/peds_neurology/17 Wed, 20 Jun 2012 11:23:00 PDT Depression is the most common psychiatric comorbidity in epilepsy. To better understand the contribution of seizures versus environment to depression in epilepsy, we investigated differential gene expression using microarray and quantitative RT-PCR, and depressive behavior, in the Porsolt forced swim test in juvenile rats reared in different environments after kainic acid (KA)-induced seizures. We selected for genes significantly down-regulated by KA seizures and upregulated by environmental enrichment. This common gene selection process yielded one known gene involved in mood and affect: serotonin receptor 5B. The changes in serotonin receptor gene expression were paralleled by decreased mobility in the forced swim tests; depressive behavior exhibited after seizures was no longer evident in rats reared in environmental enrichment. Our results suggest that seizures lead to increased susceptibility to depression through transcriptional regulation while environment, in turn, can interact with gene expression to influence the behavioral outcome of epilepsy.

]]> Sookyoung Koh et al. Analysis of Variance Animals Animals, Newborn Behavior, Animal Depressive Disorder Down-Regulation *Environment Kainic Acid Microarray Analysis Rats Rats, Long-Evans Receptors, Serotonin Seizures Swimming DNA targeting of rhinal cortex D2 receptor protein reversibly blocks learning of cues that predict reward http://escholarship.umassmed.edu/peds_neurology/15 http://escholarship.umassmed.edu/peds_neurology/15 Wed, 20 Jun 2012 11:22:56 PDT When schedules of several operant trials must be successfully completed to obtain a reward, monkeys quickly learn to adjust their behavioral performance by using visual cues that signal how many trials have been completed and how many remain in the current schedule. Bilateral rhinal (perirhinal and entorhinal) cortex ablations irreversibly prevent this learning. Here, we apply a recombinant DNA technique to investigate the role of dopamine D2 receptor in rhinal cortex for this type of learning. Rhinal cortex was injected with a DNA construct that significantly decreased D2 receptor ligand binding and temporarily produced the same profound learning deficit seen after ablation. However, unlike after ablation, the D2 receptor-targeted, DNA-treated monkeys recovered cue-related learning after 11-19 weeks. Injecting a DNA construct that decreased N-methyl-d-aspartate but not D2 receptor ligand binding did not interfere with learning associations between the cues and the schedules. A second D2 receptor-targeted DNA treatment administered after either recovery from a first D2 receptor-targeted DNA treatment (one monkey), after N-methyl-d-aspartate receptor-targeted DNA treatment (two monkeys), or after a vector control treatment (one monkey) also induced a learning deficit of similar duration. These results suggest that the D2 receptor in primate rhinal cortex is essential for learning to relate the visual cues to the schedules. The specificity of the receptor manipulation reported here suggests that this approach could be generalized in this or other brain pathways to relate molecular mechanisms to cognitive functions.

]]> Zheng Liu et al. Animals Autoradiography Cues DNA, Recombinant Entorhinal Cortex Gene Targeting Learning Macaca mulatta Photic Stimulation Receptors, Dopamine D2 *Reward A new gene, EVC2, is mutated in Ellis-van Creveld syndrome http://escholarship.umassmed.edu/peds_neurology/14 http://escholarship.umassmed.edu/peds_neurology/14 Wed, 20 Jun 2012 11:22:52 PDT Ellis-van Creveld syndrome (EvC; MIM 225500) is an autosomal recessive chondrodysplastic dwarfism. Thus far, the identified mutations in the EVC gene located on chromosome 4p16 have only accounted for illness in a small proportion of affected individuals. In this report we describe a novel gene, EVC2, that is mutated in an Ashkenazi individual with EvC syndrome. Our findings demonstrate for the first time that the heterogeneity observed in this disorder is not solely the result of mutations in a single gene.

]]> Marzena Galdzicka et al. Ellis-Van Creveld Syndrome Female Genetic Heterogeneity Humans *Jews Male Pedigree Proteins Sequence Analysis, DNA Glucosylsphingosine accumulation in tissues from patients with Gaucher disease: correlation with phenotype and genotype http://escholarship.umassmed.edu/peds_neurology/13 http://escholarship.umassmed.edu/peds_neurology/13 Wed, 20 Jun 2012 11:22:47 PDT Gaucher disease, the inherited deficiency of lysosomal glucocerebrosidase, presents with a wide spectrum of clinical manifestations including neuronopathic and non-neuronopathic forms. While the lipid glucosylceramide is stored in both patients with Gaucher disease and in a null allele mouse model of Gaucher disease, elevated levels of a second potentially toxic substrate, glucosylsphingosine, are also found. Using high performance liquid chromatography, glucosylsphingosine levels were measured in tissues from patients with type 1, 2, and 3 Gaucher disease. Glucosylsphingosine was measured in 16 spleen samples (8 type 1; 4 type 2; and 4, type 3) and levels ranged from 54 to 728 ng/mg protein in the patients with type 1 disease, 133 to 1200 ng/mg protein in the patients with type 2, and 109 to 1298 ng/mg protein in the type 3 samples. The levels of splenic glucosylsphingosine bore no relation to the type of Gaucher disease, the age of the patient, the genotype, nor the clinical course. In the same patients, hepatic glucosylsphingosine levels were lower than in spleen. Glucosylsphingosine was also measured in brains from 13 patients (1 type 1; 8 type 2; and 4 type 3). While the glucosylsphingosine level in the brain from the type 1 patient, 1.0 ng/mg protein, was in the normal range, the levels in the type 3 samples ranged from 14 to 32 ng/mg protein, and in the type 2 samples from 24 to 437 ng/mg protein, with the highest values detected in two fetuses with hydrops fetalis. The elevated levels found in brains from patients with neuronopathic Gaucher disease support the hypothesis that glucosylsphingosine may contribute to the nervous system involvement in these patients.

]]> Eduard Orvisky et al. Adolescent Adult Brain Child Child, Preschool Chromatography, High Pressure Liquid Female Gaucher Disease Genotype Humans Infant Liver Male Middle Aged Organ Specificity Phenotype Psychosine Sphingosine Spleen Structure-Activity Relationship Vasopressin V1b receptor knockout reduces aggressive behavior in male mice http://escholarship.umassmed.edu/peds_neurology/12 http://escholarship.umassmed.edu/peds_neurology/12 Wed, 20 Jun 2012 11:22:43 PDT Increased aggression is commonly associated with many neurological and psychiatric disorders. Current treatments are largely empirical and are often accompanied by severe side effects, underscoring the need for a better understanding of the neural bases of aggression. Vasopressin, acting through its 1a receptor subtype, is known to affect aggressive behaviors. The vasopressin 1b receptor (V1bR) is also expressed in the brain, but has received much less attention due to a lack of specific drugs. Here we report that mice without the V1bR exhibit markedly reduced aggression and modestly impaired social recognition. By contrast, they perform normally in all the other behaviors that we have examined, such as sexual behavior, suggesting that reduced aggression and social memory are not simply the result of a global deficit in sensorimotor function or motivation. Fos-mapping within chemosensory responsive regions suggests that the behavioral deficits in V1bR knockout mice are not due to defects in detection and transmission of chemosensory signals to the brain. We suggest that V1bR antagonists could prove useful for treating aggressive behavior seen, for example, in dementias and traumatic brain injuries.

]]> S. R. Wersinger et al. Age Factors Aggression Animals Behavior, Animal Body Temperature Brain Chemistry Corticosterone Eating Exploratory Behavior Female Male Maze Learning Mice Mice, Inbred C57BL Mice, Knockout Motor Activity Neurons Phenotype Proto-Oncogene Proteins c-fos Receptors, Vasopressin Recognition (Psychology) Sexual Behavior, Animal Stress, Physiological Testosterone Visual Perception Absence of hippocampal sclerosis in children with multiple daily seizures since infancy http://escholarship.umassmed.edu/peds_neurology/11 http://escholarship.umassmed.edu/peds_neurology/11 Wed, 20 Jun 2012 11:22:39 PDT We report a series of nine children with multiple daily seizures since infancy who underwent functional hemispherectomy that included en bloc resection of the hippocampus and the temporal neocortex. In all cases, the hippocampi were normal by conventional histology despite the fact that these patients had suffered from recurrent seizures over a long period of time. This observation suggests that extremely frequent seizures in childhood are not invariably associated with the development of hippocampal sclerosis.

]]> Sanjeev V. Kothare et al. Child Child, Preschool Electroencephalography Epilepsy, Temporal Lobe Hippocampus Humans Infant Magnetic Resonance Imaging Neurosurgical Procedures Periodicity Retrospective Studies Sclerosis Temporal Lobe Absence of a significant linkage between Na(+),K(+)-ATPase subunit (ATP1A3 and ATP1B3) genotypes and bipolar affective disorder in the old-order Amish http://escholarship.umassmed.edu/peds_neurology/10 http://escholarship.umassmed.edu/peds_neurology/10 Wed, 20 Jun 2012 11:22:34 PDT Previous studies provide evidence for a genetic component for susceptibility to bipolar affective disorder (BPAD) in the old-order Amish population. El-Mallakh and Wyatt [1995: Biol Psychiatry 37:235-244] have suggested that the Na(+),K(+)-ATPase may be a candidate gene for BPAD. This study examines the relationship between BPAD in the old-order Amish cohort and the Na(+),K(+)-ATPase alpha1 and beta3 subunit genes (ATP1A3, ATP1B3). A total of 166 sibling pairs were analyzed for linkage via nonparametric methods. Suggestive levels of statistical significance were not reached in any stratification model for affective illness. Overall, the results do not support linkage of bipolar disorder to the Na(+),K(+)-ATPase alpha subunit gene (ATP1A3) and beta subunit gene (ATP1B3) in these old-order Amish families and they show that these Na(+),K(+)-ATPase subunit genes are not major effect genes (>or=fourfold increased genetic risk of disease) for BPAD in the old-order Amish pedigrees. We cannot exclude other genetic variants of the Na(+),K(+)-ATPase hypothesis for BPAD, whereby other loci may modifying Na(+),K(+)-ATPase activity.

]]> Robert A. Philibert et al. Bipolar Disorder Case-Control Studies Cohort Studies Ethnic Groups *Genetic Linkage Genetic Predisposition to Disease Genotype Humans Nuclear Family Protein Subunits Sodium-Potassium-Exchanging ATPase Statistics, Nonparametric