Biomedical subjects

R S Greenwood

Publications and source records attributed to R S Greenwood.

At least 19 recordsLinked to original sources

PubMed2001

Outcome in children with fetal mild ventriculomegaly: a case series.

Mild enlargement of the lateral ventricles is associated with schizophrenia and other neurodevelopmental disorders. While it has been hypothesized that ventricle abnormalities associated with neurodevelopmental disorders arise during fetal brain development, there is little direct evidence to support this hypothesis. Using ultrasound, it is possible to image the fetal ventricles in utero. Fetal mild ventriculomegaly (MVM) has been associated with developmental delays in early childhood, though longer-term neurodevelopmental outcome has not been studied. Follow-up of five children (aged 4--9 years) with mild enlargement of the lateral ventricles on prenatal ultrasound and two unaffected co-twins is reported: one child had attention deficit hyperactivity disorder (ADHD), one had autism, and two had evidence of learning disorders. These cases suggest that the mild enlargement of the lateral ventricles associated with these neurodevelopmental disorders arises during fetal brain development and can be detected with prenatal ultrasound. In addition, the presence of mildly enlarged, asymmetric ventricles in two children on prenatal ultrasound and on follow-up MRI at age 6 years indicates that ventricle structure present in utero can persist well into childhood brain development. The study of fetal ventricle development with ultrasound may provide important insights into neurodevelopmental disorders and allow the identification of children at high risk.

Attention Deficit Disorder with Hyperactivity↗

PubMed2001

Increased brain apparent diffusion coefficient in children with neurofibromatosis type 1.

PURPOSE: To describe the changes in brain water diffusibility in five anatomic locations in children with neurofibromatosis type 1 (NF 1) compared with these changes in control subjects and to describe the water diffusibility changes associated with hyperintense basal ganglia lesions in children with NF 1. MATERIALS AND METHODS: Twenty highly related pairs of children consisting of one child with NF 1 and one unaffected child were examined. Prospective comparisons of isotropic apparent diffusion coefficient (ADC) values at five anatomic locations were performed, with and without T2-hyperintense lesions included. Retrospective analysis of hyperintense globus pallidus lesions in 16 children and in the paired control subjects also was performed. RESULTS: Significant increases in ADC values were seen in all five anatomic locations in the NF 1 group. The greatest increases were seen in the globus pallidus (14%; P =.002) and brachium pontis (10.8%; P =.003). With exclusion of hyperintense lesions, significant ADC increases were measured in four locations. Significant ADC increases were seen in hyperintense globus pallidus lesions in the NF 1 group compared with ADC values in the normal-appearing contralateral globus pallidus (4.9%; P =.02) and those in the globus pallidus of the paired control subjects (16%; P =.003). CONCLUSION: Significant ADC increases were measured both in the hyperintense lesions and in the normal-appearing areas of the brain in children with NF 1.

Adolescent↗

PubMed2000

Successful treatment of hypothalamic seizures and precocious puberty with GnRH analogue.

Patients with hypothalamic hamartomas and precocious puberty may develop gelastic seizures that are resistant to conventional antiepileptic drug therapies. While treating precocious puberty in two such patients with long-acting GnRH analogue, the authors observed cessation of gelastic seizures. Although the mechanism is unclear, long-acting GnRH analogue should be considered as a possible therapy for gelastic seizures in patients with hypothalamic hamartomas.

Adolescent↗

PubMed2000

Inhibition of hippocampal kindling by metabotropic glutamate receptor antisense oligonucleotides.

Recent work has shown that metabotropic glutamate receptors (mGluRs) increase in response to seizure activity and can contribute significantly to the expression and progression of partial seizures. Using the kindling model of temporal lobe seizures, we evaluated the ability of local hippocampal injections of mGluR1 antisense or mGluR3 antisense oligonucleotides to suppress receptor expression and alter hippocampal kindling. Daily antisense injections in the hippocampus resulted in a significant decrease in mGluR1 or mGluR2/3 immunoreactivity. Rats injected with mGluR3 antisense showed a brief suppression of afterdischarge duration when compared to matched rats injected with a nonsense-oligonucleotide. Rats injected with a mGluR1 antisense oligonucleotide had a dramatic suppression of the rate of seizure progression with no significant effect on afterdischarge duration. Suppression of mGluR1 synthesis by local antisense inhibition may provide a new therapeutic approach for the control of epileptogenesis.

Animals↗

PubMed2000

Adverse effects of antiepileptic drugs.

Because the efficacies of antiepileptic drugs (AEDs) are often equivalent, selection of an AED is often determined by adverse effects. Differences in methods for labeling adverse effects and in the adverse effect terms themselves, variations in the populations studied, and inconsistent classifications of adverse effects make it difficult to know how to use information on adverse effects to choose an AED. Effort is underway to develop more extensive and internationally acceptable descriptive terms for adverse effects. Comparison of adverse effects in patients taking AEDs with adverse events in control groups is helpful; however, data from controlled studies are often lacking for most AEDs. Because of these limitations, the clinician must adopt a preventative and early detection approach based on some general principles. This review outlines factors to consider for avoiding and detecting AED adverse effects. The occurrence of weight change with AEDs is reviewed extensively, serving to illustrate how the principle factors can be used to avoid and manage adverse effects and where there is need for better studies of the short- and long-term adverse effects of AEDs.

Acute Disease↗

PubMed1999

When to start and stop anticonvulsant therapy in children.

A large body of evidence has accrued in recent years, allowing a more precise estimate of the risk of seizure recurrence for children with new-onset seizures and for children who stop therapy once they are seizure-free. The primary goal for children with epilepsy is not solely freedom from seizures, but an optimal quality of life. Unless the physician can predict a recurrence risk at the extremes (0% or 100%), the nonmedical factors that affect quality of life will usually dominate the family's decision making. Together, the physician and family should weigh the risks and benefits of treatment against the risks and benefits of withholding or stopping therapy. Antiepileptic drug treatment should be withheld from most children until they have had a second seizure. Most children who receive antiepileptic drug treatment should attempt to taper their medications after 2 years without seizures.

Anticonvulsants↗

PubMed1998

Kindled seizures increase metabotropic glutamate receptor expression and function in the rat supraoptic nucleus.

The spread of experimentally kindled seizures in rats results in sustained increases in plasma vasopressin (VP) and VP mRNA in the supraoptic nucleus (SON). These increases provide an excellent example of the pathological plasticity that can develop in normal cells exposed to recurrent seizure activity. To test whether this plasticity might be due in part to changes in metabotropic glutamate receptors (mGluRs), we examined mGluR mRNA expression in the SON 1 month after stage 5 amygdala kindling. Three mGluR subtypes were detected by in situ hybridization in the SON in the following relative levels: mGluR3 > mGluR1 > mGluR7. Both mGluR1 and mGluR3 mRNAs were significantly increased in the SON (+28-61%) and cortex (+27-42%) after kindling. Immunoreactivity for mGluR1 but not mGluR2/3 was significantly increased in vivo in the SON. Receptor protein expression and intracellular calcium accumulation in response to the mGluR agonist, 1S,3R ACPD, were evaluated after in vitro "kindling" of neuroendocrine cells by Mg2+ deprivation. Increased immunoreactivity for mGluR1 and mGluR2/3 was seen in all cultures 3 days after a brief exposure to Mg2+-free medium. 1S,3R 1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) induced rapid peak responses and gradual accumulations of intracellular Ca2+ in neurons. Both responses were increased in the "kindled" cells. Increases in the expression of functional mGluR1 and perhaps mGluR3 receptors may contribute to the development of long-lasting plastic changes associated with seizure activity.

Amygdala↗

PubMed1998

The mitochondrial DNA A8344G mutation in Leigh syndrome revealed by analysis in paraffin-embedded sections: revisiting the past.

In 1975, we presented the results of a study on a family with a constellation of features that included a chronic spinocerebellar syndrome, neuropathologically proven Leigh syndrome, and sudden death in infancy or childhood affecting several members over three generations. Inheritance was thought to be autosomal dominant. Twenty years later, we reinterpreted the inheritance pattern as maternal. Mitochondrial DNA (mtDNA) extracted from paraffin-embedded brain samples from the proband revealed the A8344G myoclonic epilepsy and ragged-red fiber (MERRF) mutation as the molecular basis for this multifaceted neurological syndrome. This re-evaluation of archival material is an instructive example of "medical archeopathology."

Adolescent↗

PubMed1998

Photoparoxysmal response in late infantile neuronal ceroid-lipofuscinosis.

A patient presented with rapid developmental regression whose MRI findings suggested a leukodystrophy, but nerve, muscle, skin, and bone marrow biopsies were unrevealing. A characteristic photoparoxysmal response on electroencephalogram provided an important clue for the correct diagnosis of late infantile neuronal ceroid-lipofuscinosis, which was confirmed later with electron microscope examination of a brain biopsy. In patients with rapid neurologic deterioration, diagnosis of neuronal ceroid-lipofuscinosis should be considered and an electroencephalogram should be performed using photic stimulation to look for characteristic findings.

Biopsy↗

PubMed1998

L-carnitine supplementation in childhood epilepsy: current perspectives.

In November 1996, a panel of pediatric neurologists met to update the consensus statement issued in 1989 by a panel of neurologists and metabolic experts on L-carnitine supplementation in childhood epilepsy. The panelists agreed that intravenous L-carnitine supplementation is clearly indicated for valproate (VPA)-induced hepatotoxicity, overdose, and other acute metabolic crises associated with carnitine deficiency. Oral supplementation is clearly indicated for the primary plasmalemmal carnitine transporter defect. The panelists concurred that oral L-carnitine supplementation is strongly suggested for the following groups as well: patients with certain secondary carnitine-deficiency syndromes, symptomatic VPA-associated hyperammonemia, multiple risk factors for VPA hepatotoxicity, or renal-associated syndromes; infants and young children taking VPA; patients with epilepsy using the ketogenic diet who have hypocarnitinemia; patients receiving dialysis; and premature infants who are receiving total parenteral nutrition. The panel recommended an oral L-carnitine dosage of 100 mg/kg/day, up to a maximum of 2 g/day. Intravenous supplementation for medical emergency situations usually exceeds this recommended dosage.

Age Factors↗

PubMed1998

Carbamazepine responsive epileptic oral motor and ocular motor apraxia.

We evaluated seven patients with oral motor apraxia and ocular motor apraxia. Apraxia in three patients (Group 1) with new-onset partial seizures and epileptiform discharges on EEG improved with carbamazepine. Four patients (Group 2) without seizures and nonepileptiform EEG findings had no change in apraxia after a trial of carbamazepine. Epileptic apraxia may precede clinical seizures and can respond to antiepileptic drugs.

Anticonvulsants↗

PubMed1998

Proton MR spectroscopy in psychiatric and neurodevelopmental childhood disorders: early experience.

Variations in brain morphology are increasingly being found in patients with psychiatric disorders. There is early evidence that some metabolic abnormalities may also be present in these patients. In many patients with psychiatric disorders, the diagnosis is not straight forward and may be confounded by co-morbid processes. Establishing the correct diagnosis is important as it leads to institution of appropriate therapies. Descriptions of the authors early experience using proton MR spectroscopy in the evaluation of children with bipolar affective disorder, attention deficit hyperactivity disorder, neurodevelopmental abnormalities in patients with neurofibromatosis type 1, and the effects of certain types of treatment used for these disorders are discussed.

Attention Deficit Disorder with Hyperactivity↗

PubMed1997

Persistent elevation of corticotrophin releasing factor and vasopressin but not oxytocin mRNA in the rat after kindled seizures.

Intractable temporal lobe epilepsy is a disabling disorder with far reaching effects on brain function, behavior and neuroendocrine function. Previous work in the kindled-seizure model for temporal lobe epilepsy has shown that these seizures cause vasopressin (VP) release, an increase in resting VP and lasting increases in VP mRNA in the supraoptic nucleus (SON) of the hypothalamus. In this study we used in situ hybridization to examine the effects of kindled seizures on the expression of two other functionally-related, neuroendocrine genes, oxytocin (OT) and corticotrophin releasing factor (CRF). Comparisons in kindled and sham-stimulated controls revealed an increase in VP mRNA but not OT mRNA in magnocellular neurons and an increase in CRF mRNA in parvocellular neurons of the paraventricular nucleus (PVN) of the hypothalamus 1 month after the last seizure. We conclude that kindled seizures induce selective changes in neuroendocrine gene expression in neuroendocrine systems, VP and CRF but not OT.

Animals↗

PubMed1997

Differential expression of five N-methyl-D-aspartate receptor subunit mRNAs in vasopressin and oxytocin neuroendocrine cells.

Vasopressin and oxytocin neuroendocrine cells within the supraoptic nucleus display distinctive electrophysiological properties and differential responses to selected NMDA receptor (NR) antagonists. To determine if these differences might be due to NMDA receptor composition, we compared the expression of NR1, NR2A, NR2B, NR2C and NR2D subunit mRNAs in immunocytochemically identified vasopressin and oxytocin neuroendocrine cells. In contrast to NR1 subunit mRNA which was equally expressed in both vasopressin and oxytocin cells, NR2B and NR2C displayed very different expression patterns. In oxytocin cells, the NR2B subunit comprised the majority (65%) of the total NR2 expression with NR2C and NR2D contributing 6% and 27%, respectively. Vasopressin cells exhibited 5-fold higher NR2C (32%), approximately half as much NR2B mRNA (39%) and equivalent NR2D (31%). In vitro expression studies have shown that the NR1-NR2C subunit combination exhibits weaker magnesium block and higher affinity for glycine than NR1-NR2B. Thus, the high expression of NR2C in vasopressin cells relative to oxytocin cells may make these cells more susceptible to glutamatergic activation. These observations in vasopressin and oxytocin cells provide the basis for a working model to investigate how differential NMDA receptor composition may shape the neurophysiological properties of neurons.

Animals↗

PubMed1997

Amygdala kindling alters N-methyl-D-aspartate receptor subunit messenger RNA expression in the rat supraoptic nucleus.

Intense electrical activity throughout the brain which results from generalized epileptic or kindled seizures is thought to cause persistent and widespread neuronal plastic changes. We have previously reported that stage 5 kindled seizures cause an increase in vasopressin messenger RNA content and nitric oxide synthase activity in neuroendocrine cells of the supraoptic nucleus which lasts for at least four months after the last seizure. To evaluate whether changes in the expression of N-methyl-D-aspartate receptor subunits might contribute to these effects, the expression of NR1, NR2A, NR2B. NR2C and NR2D subunit messenger RNAs was examined by in situ hybridization in neuroendocrine cells of the supraoptic nucleus one month after amygdala kindling to stage 5 seizures. No change in NR1 subunit messenger RNA expression was seen. In contrast, NR2B subunit messenger RNA was significantly increased. by about 63%, and NR2D subunit messenger RNA was significantly decreased, by about 22%. indicating a shift in NR2 subunit messenger RNA expression. NR2B subunit messenger RNA was also significantly increased in adjacent limbic structures. The long-lasting shift towards increased NR2B and decreased NR2D messenger RNA expression after kindling suggests that N-methyl-D-aspartate receptor NR2 composition may be an important factor in the maintenance of pathological plasticity following generalized seizures. If these changes in messenger RNA are translated into increased NR2B and decreased NR2D subunits in the N-methyl-D-aspartate receptors in vivo, both a decrease in sensitivity due to a strong magnesium block and an increase in channel ion gating might be predicted.

Amygdala↗

PubMed1996

MRI morphometric analysis and neuropsychological function in patients with neurofibromatosis.

Volumes of cerebral gray and white matter were measured in 22 children with neurofibromatosis type 1 (NF1) and in 20 controls. Judgment of Line Orientation (JLO) and the Developmental Test of Visual-Motor Integration (DTVMI) were administered to 16 of the NF1 patients. General linear models analysis of covariance revealed significantly larger brain volumes in NF1 children than in controls, particularly in white matter, and particularly in girls. JLO and DTVMI performance were positively related to right-hemisphere gray-matter volume. The results implicate a failure of growth control in NF1, leading to aberrant neurodevelopment. Our findings also suggest a basis for refined understanding of learning disabilities, which are a prominent feature of NF1.

Adolescent↗

PubMed1996

Similarities of EEG and seizures in del(1q) and benign rolandic epilepsy.

We studied the seizure disorders manifested by three previously reported children with "de novo" terminal deletions of the long arm of chromosome 1 (46,XX,del(1)(q43)) and similar clinical phenotypes. In late infancy, two of these children developed partial seizures characterized by tonic-clonic movements of the ipsilateral face and arm with occasional involvement of the leg. In both children, the seizure frequency decreased with increasing age. Electroencephalograms of these two children demonstrated centrotemporal spike discharges morphologically similar to rolandic spikes. Although these cases present significant similarities to benign rolandic epilepsy, they also express many manifestations not detected in benign rolandic epilepsy that may reflect the extensive deletion of chromosome 1. Based on the seizure semiology and centrotemporal epileptiform discharges, we suggest that the distal portion of the long arm of chromosome 1 is a potential site for a candidate gene for benign rolandic epilepsy.

Age Factors↗

PubMed1995

Kindling induces a long-lasting increase in brain nitric oxide synthase activity.

Generalized seizures induced by kindling are associated with a long-term increase in vasopressin mRNA expression in vasopressin neuroendocrine cells. Since nitric oxide synthase activity is strongly expressed in these neurons and may play a role in mechanisms of plasticity, we used NADPH-diaphorase histochemistry to examine nitric oxide synthase activity 1 month after amygdala kindling. Both the number of stained neurons and average intensity of cellular labeling in the supraoptic nucleus were increased in the kindled rats. In adjacent limbic regions, terminal-like staining was also increased, suggesting a general elevation of limbic nitric oxide synthase activity. Thus, increased nitric oxide production may play a role in sustaining the increase in vasopressin mRNA and plastic changes in the amygdala associated with kindling.

Amino Acid Oxidoreductases↗