Biomedical subjects

Shenandoah Robinson

Publications and source records attributed to Shenandoah Robinson.

12 recordsLinked to original sources

PubMed2006

Regional metabolic status of the E-18 rat fetal brain following transient hypoxia/ischemia.

Increasing evidence indicates that fetal metabolic stress may result in a variety of post-natal perturbations during brain development. The goal of the study was to determine the duration of hypoxia/ischemia that would elicit a demonstrable regional depression of metabolism in the fetal brain and further to examine several end-points to determine if the metabolic stress affects the developing brain. The uterine artery and uterine branch of the ovarian artery were occluded with aneurysm clamps for a period of 45 min, the clips removed and the metabolites in five regions of the perinatal brain were measured at 0, 2 and 6 h of reflow. Regional P-creatine, ATP and glucose levels were significantly depleted at the end of the 45 min occlusion. The levels of glycogen and glutamate at the end of the occlusion indicated a decreasing trend which was not significant. The concentration of citrate remained essentially unchanged at the end of the occlusion. To ensure that the insult was not lethal to the tissue, the recovery of the metabolites was examined at 2 and 6 h of reflow and generally the concentrations of the high-energy phosphates and glucose were normal or near-normal by 6 h of reperfusion in the five regions of the brain examined. The changes in the metabolites indicate that 45 min of hypoxia/ischemia is an appropriate model for studying neonatal development after fetal metabolic stress.

Adenosine Triphosphate↗

PubMed2006

Cowden disease and Lhermitte-Duclos disease: an update. Case report and review of the literature.

OBJECT: Cowden disease is a rare autosomal-dominant phacomatosis and cancer syndrome that is associated with Lhermitte-Duclos disease (LDD), also called dysplastic cerebellar gangliocytoma. METHODS: In this review the authors summarize the additions to the literature during the past 5 years, with emphasis on new case reports and advances in imaging and molecular biology. Adult-onset LDD is now considered pathognomonic for Cowden disease. Approximately 220 cases of LDD have been reported. Magnetic resonance imaging in patients with LDD is often diagnostic, and imaging studies have facilitated accurate diagnosis and contributed to the improved outcome in affected patients. Cowden disease and other rare, related disorders, such as Bannayan-Riley-Ruvalcaba, Proteus, and Proteus- like syndromes, are often caused by mutations of the PTEN gene. CONCLUSIONS: Because of the high incidence of systemic cancer in patients with Cowden disease, it is important for neurosurgeons to recognize the association between this disease and LDD and to refer affected patients for appropriate cancer screenings and interventions.

Adolescent↗

PubMed2006

Neonatal loss of gamma-aminobutyric acid pathway expression after human perinatal brain injury.

OBJECT: Perinatal brain injury leads to chronic neurological deficits in children. Damage to the premature brain produces white matter lesions (WMLs), but the impact on cortical development is less well defined. Gamma-aminobutyric acid(GABA)ergic neurons destined for the cerebral cortex migrate through the developing white matter and form the subplate during late gestation. The authors hypothesized that GABAergic neurons are vulnerable to perinatal systemic insults in premature infants, and that damage to these neurons contributes to impaired cortical development. METHODS: An immunohistochemical analysis involving markers for oligodendrocytes, GABAergic neurons, axons, and apoptosis was performed on a consecutive series of 15 human neonatal telencephalon samples obtained postmortem from infants born at 25 to 32 weeks of gestation. The tissue samples were divided into two groups based on the presence or absence of WMLs by performing routine histological analyses. The expression of GABAergic neurons was compared between the two groups by using age-matched samples. Two-tailed t-tests were used for statistical analyses. Ten infants had WMLs and five did not. Significant losses of oligodendrocytes and axons and markedly increased apoptosis were appreciated in tissue samples from the infants with WMLs. Samples from infants with WMLs also showed significant losses of glutamic acid decarboxylase-67-positive cells and calretinin-positive cells, shorter neuropeptide Y-positive neurite lengths, and losses of cells expressing GABA(A)alpha1, GABA(B)R1, and N-acetylaspartate diethylamide NR1 receptors when these factors were compared with those in samples from infants without WMLs (all p < 0.02). CONCLUSIONS: In addition to oligodendrocyte loss, axonal disruption, and excess apoptosis, a significant loss of telencephalon GABAergic neuron expression was found in neonatal brains with WMLs, compared with neonates' brains without WMLs. The loss of GABAergic subplate neurons in infants with WMLs may contribute to the pathogenesis of neurological deficits in children.

Calbindin 2↗

PubMed2005

Systemic prenatal insults disrupt telencephalon development: implications for potential interventions.

Infants born prematurely are prone to chronic neurologic deficits including cerebral palsy, epilepsy, cognitive delay, behavioral problems, and neurosensory impairments. In affected children, imaging and neuropathological findings demonstrate significant damage to white matter. The extent of cortical damage has been less obvious. Advances in the understanding of telencephalon development provide insights into how systemic intrauterine insults affect the developing white matter, subplate, and cortex, and lead to multiple neurologic impairments. In addition to white matter oligodendrocytes and axons, other elements at risk for perinatal brain injury include subplate neurons, GABAergic neurons migrating through white matter and subplate, and afferents of maturing neurotransmitter systems. Common insults including hypoxia-ischemia and infection often affect the developing brain differently than the mature brain, and insults precipitate a cascade of damage to multiple neural lineages. Insights from development can identify potential targets for therapies to repair the damaged neonatal brain before it has matured.

Adult↗

PubMed2005

Developmental changes induced by graded prenatal systemic hypoxic-ischemic insults in rats.

In infants, a common consequence of systemic perinatal insults is disruption of neonatal brain development. Such insults can cause cerebral palsy, cognitive delay, epilepsy and other chronic neurologic deficits in children. The mechanisms underlying disruption of brain development after perinatal insults are poorly defined. To mimic human systemic insults, a transient prenatal hypoxic-ischemic insult model was developed in rodents. Ischemic animals showed reproducible histological lesions including oligodendrocyte loss, gliosis, and axonal disruption. Ischemic animals displayed persistent postnatal loss of oligodendrocyte lineage cells and cortical neurons, decreased cell proliferation, increased cell death, elevated pro-inflammatory cytokine levels, and impaired motor skills as young adults. Progressive ischemic intervals produced a graded pattern of injury. This systemic rodent prenatal hypoxic-ischemic insult accurately models human perinatal brain injury in several important criteria, including functional association of altered brain development with motor delay, and consequently provides novel insights into the pathogenesis of human perinatal brain insults.

Animals↗

PubMed2005

Insights into meningioangiomatosis with and without meningioma: a clinicopathologic and genetic series of 24 cases with review of the literature.

Meningioangiomatosis (MA) is a rare seizure-associated lesion of presumed hamartomatous or developmental origin. It is occasionally combined with a neoplasm, most commonly meningioma (MA-M). In the current study, we examined 24 cases (14 pure MA, 10 MA-M) using immunohistochemistry for merlin, protein 4.1 B, progesterone receptor (PR), and MIB-1, as well as FISH for NF2 and 4.1B gene dosages. Nine cases of MA-M (90%) had gene deletions (NF2/4.7B), protein losses (merlin/protein 4.1B), and/or PR positivity, with a similar or identical phenotype in both components. No PR positivity or gene deletions were seen in pure MAs, though merlin and/or protein 4.1B were immunonegative in six cases. Our data suggest that in most MA-Ms, the MA component is neoplastic, likely representing an exuberant perivascular pattern of spread from the meningioma, rather than an underlying hamartoma. This pattern of spread may be facilitated by meningiomas that are predominantly leptomeningeal or intracerebral in origin. It remains important to distinguish this pattern from true brain invasion, given the more ominous prognostic significance of the latter. In contrast, most perivascular spindled cells of pure MA are genetically and immunohistochemically similar to non-neoplastic meningothelial cells, consistent with current histogenetic theories.

Adolescent↗

PubMed2005

Pineal region giant cell astrocytoma associated with tuberous sclerosis: case report.

Tuberous sclerosis complex is a genetic disorder characterized by the development of hamartomas in multiple organs including the brain, skin, eye, kidney, and heart. Neurological features include seizures and mental retardation. Cortical tubers and subependymal nodules are the characteristic intracranial lesions of tuberous sclerosis. Subependymal giant cell astrocytomas, typically located adjacent to the foramen of Monro, can enlarge and cause symptomatic ventricular obstruction. The authors describe the case of a 3-year-old boy with a history of tuberous sclerosis and retinal lesions who presented with an enlarging enhancing pineal region mass. Via an infratentorial supracerebellar approach, the mass was removed using both the operative microscope and a rigid neuroendoscope. Pathological examination showed a giant cell astrocytoma. To the authors' knowledge, this is the first reported case of tuberous sclerosis associated with a giant cell astrocytoma of the pineal region. Diagnostic considerations are discussed.

Astrocytoma↗

PubMed2004

High-resolution MRI enhances identification of lesions amenable to surgical therapy in children with intractable epilepsy.

PURPOSE: Many children with refractory epilepsy can achieve better seizure control with surgical therapy. An abnormality on magnetic resonance imaging (MRI), along with corroborating localization by other modalities, markedly increases chances of successful surgical outcome. We studied the impact of high-resolution MRI on the surgical outcome of intractable epilepsy. METHODS: High-resolution MRI using four-coil phased surface array was obtained as part of the comprehensive presurgical protocol for children with focal onset intractable seizures evaluated by our epilepsy center during the first half of 2002. RESULTS: Thirteen consecutive children, ages 5 to 18 years, entered this prospective study. For four patients with a lesion on a recent MRI examination with a standard head coil, management did not change with high-resolution MRI. Standard MRI in the other nine patients did not identify a lesion. However, high-resolution MRI with the phased-array surface coil found previously undiagnosed focal abnormalities in five of nine patients. These abnormalities included hippocampal dysplasia, hippocampal atrophy, and dual pathology with frontal cortical dysplasia. In four of nine patients, no identifiable lesion was identified on the high-resolution MRI. All patients underwent invasive monitoring. In three of five patients, newly diagnosed lesions correlated with EEG abnormalities, and resection was performed. CONCLUSIONS: In our center, high-resolution MRI identified lesions not detected by standard MRI in more than half the children (56%). Technical advances such as four-coil phased surface array MRI can help identify and better delineate lesions, improving the diagnosis of patients who are candidates for surgical treatment of refractory epilepsy.

Adolescent↗

PubMed2002

The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration.

Spinal cord oligodendrocytes originate in the ventricular zone and subsequently migrate to white matter, stop, proliferate, and differentiate. Here we demonstrate a role for the chemokine CXCL1 and its receptor CXCR2 in patterning the developing spinal cord. Signaling through CXCR2, CXCL1 inhibited oligodendrocyte precursor migration. The migrational arrest was rapid, reversible, concentration dependent, and reflected enhanced cell/substrate interactions. White matter expression of CXCL1 was temporo-spatially regulated. Developing CXCR2 null spinal cords contained reduced oligodendrocytes, abnormally concentrated at the periphery. In slice preparations, CXCL1 inhibited embryonic oligodendrocyte precursor migration, and widespread dispersal of postnatal precursors occurred in the absence of CXCR2 signaling. These data suggest that population of presumptive white matter by oligodendrocyte precursors is dependent on localized expression of CXCL1.

Animals↗

PubMed2002

Atypical teratoid/rhabdoid tumors of the central nervous system: clinical, radiographic and pathologic features.

INTRODUCTION: Atypical teratoid/rhabdoid tumors (ATT/RT) of the central nervous system (CNS) are uncommon malignancies of childhood with an aggressive course and a uniformly fatal outcome. METHODS: The medical records, radiographic images and pathologic files at the Rainbow Babies and Childrens Hospital over the previous 6 years were retrospectively reviewed. RESULTS: Eight children underwent surgery for CNS ATT/RT at our institution since 1996. There were 6 boys and 2 girls. Median age at presentation was 21 months. Four tumors had multifocal disease at the time of diagnosis. Six patients received multiagent chemotherapy including 3 patients with autologous bone marrow transplantation, and 6 patients received radiation therapy. Median survival was 9 months from the time of diagnosis. CONCLUSIONS: In spite of aggressive therapy, the prognosis for ATT/RT remains dismal. The search for effective treatment strategies will require a better understanding of the biology and molecular genetics of this tumor.

Adolescent↗

PubMed2002

Outcome analysis of initial neonatal shunts: does the valve make a difference?

OBJECTIVE: Ventriculoperitoneal shunts have one of the highest complication rates of all neurosurgical procedures. The purpose of this study was to identify factors associated with malfunction of shunts placed in infants with neonatal hydrocephalus, with the goal of maximizing long-term shunt survival. METHODS: We performed a retrospective chart review of 200 consecutive patients less than 1 year old who underwent primary intracranial shunt placement for hydrocephalus by one of two experienced pediatric neurosurgeons at a single institution. A multivariate analysis was conducted to identify variables that were statistically independent predictors of a shunt malfunction or problem. RESULTS: Adequate data were available for 158 patients, with a mean follow-up of 39.8 months (range 6-99 months). Variables tested for independent prediction of shunt revision included the etiology of the hydrocephalus, gestation period, age at shunt placement, surgeon, ventricular catheter entry site and valve opening pressure. Frontal versus occipital catheter entry site was not associated with a different revision rate. The only significant controllable factor associated with shunt malfunction was the valve opening pressure. The revision rate per year of follow-up was 4 times higher for patients with no valve or a low-pressure valve than for patients with a medium- or high-pressure valve. CONCLUSIONS: This retrospective review demonstrated that the valve opening pressure is an important component of the shunt complication rate. A prospective multicenter randomized trial is warranted to further evaluate the conclusions of this study.

Age Factors↗

PubMedDate not supplied

Sledding accidents in children: potential for serious injury, risk of fatality.

Though a pastime rarely considered rough or dangerous, sledding is not risk-free. The presentation of several serious injuries to Rainbow Babies and Children's Hospital in Cleveland, Ohio, led us to examine our emergency department and admitting records to determine the incidence of neurological injury among children involved in sledding accidents. We discovered 24 children who had sustained brain or spine injuries as sequelae to sledding mishaps during a 5-year period. The ages ranged from 3 months to 15 years. Injuries included multiple skull fractures, 2 epidural hematomas, 1 subdural hematoma, 1 odontoid fracture and 1 anoxic brain injury. There was 1 death. Twenty-one of 24 patients incurred their injuries by colliding with fixed objects. Both improvised crafts and models intended for sledding were involved in the injuries. Only 3 sleds possessed steering capability. Eight of the 9 children who sustained a serious neurosurgical injury were supervised by an adult. Only 2 children had received instruction before sledding. The lack of awareness of the potential for injury together with the dearth of instruction and lack of control over a vehicle dashing down a hill studded with obstacles can change a carefree pastime into a hazardous activity.

Accidents↗