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Biomedical subjects

P Ellen Grant

Publications and source records attributed to P Ellen Grant.

At least 19 recordsLinked to original sources
PubMed2006

Acute injury to the immature brain with hypoxia with or without hypoperfusion.

This article reviews the imaging features and evolution of immature brain injury caused by hypoxia with or without hypoperfusion in the neonate and young child. Clinical presentations and available literature on mechanisms and clinical outcomes are discussed. In many of these cases, diffusion-weighted imaging does not show the full extent of the injury but detects a pattern of injury that is important in guiding clinical care. Awareness of the delayed cell death mechanisms is essential to understand diffusion-weighted imaging sensitivity and evolution and to provide the most accurate clinical interpretation, especially in cases of hypoxia with or without hypoperfusion.

Age Factors↗
PubMed2005

Pediatric stroke: the child is not merely a small adult.

Arterial ischemic stroke and sinovenous thrombosis are a significant yet under-recognized causes of mortality and morbidity in the pediatric population. With increasingly complex etiologies yet urgency for rapid diagnosis and treatment, pediatric stroke teams likely will become the standard of care. A common terminology must be developed to avoid confusing types of acute cerebral insults--such as focal arterial ischemic stroke and global hypoxia and ischemia--that have different causes and pathophysiologic mechanisms of injury. Increased awareness of unique pediatric stroke subtypes, their clinical presentation, and their imaging findings will facilitate early identification and development of optimal treatment strategies.

Adolescent↗
PubMed2005

Imaging the developing epileptic brain.

Accurate identification of cortical malformations in children with epilepsy can be crucial for successful clinical management. Although standard head-coil magnetic resonance imaging (MRI) at 1.5 tesla (T) can be used to view the macrostructure of the brain, phased array technology at both 1.5 and 3T significantly improves signal-to-noise ratio (SNR). As a result, spatial resolution and contrast can be optimized to increase visual detection of subtle macrostructural changes that occur with small epileptogenic lesions. In addition, these improvements in SNR allow more accurate quantitative analysis of brain macrostructure and more accurate assessment of brain microstructure using newer sophisticated imaging techniques. For example, phased array imaging enables more accurate diffusion tensor imaging (DTI), and 3T imaging, when combined with phased array technology, enables more informative diffusion spectroscopic imaging (DSI). Recent technological improvements therefore result in improved lesion detection and enable assessment of cerebral growth trajectories and associated longitudinal changes in tissue microstructural organization that occur in association with various types of epilepsy. This article presents a brief comparison of imaging techniques currently in use, both clinically and experimentally, to diagnose, treat, and increase our understanding of the neuropathology of epilepsy in the developing brain.

Adult↗
PubMed2005

Structural brain magnetic resonance imaging of limbic and thalamic volumes in pediatric bipolar disorder.

BACKGROUND: Youths with bipolar disorder are ideal for studying illness pathophysiology given their early presentation, lack of extended treatment, and high genetic loading. Adult bipolar disorder MRI studies have focused increasingly on limbic structures and the thalamus because of their role in mood and cognition. On the basis of adult studies, the authors hypothesized a priori that youths with bipolar disorder would have amygdalar, hippocampal, and thalamic volume abnormalities. METHOD: Forty-three youths 6-16 years of age with DSM-IV bipolar disorder (23 male, 20 female) and 20 healthy comparison subjects (12 male, eight female) similar in age and sex underwent structured and clinical interviews, neurological examination, and cognitive testing. Differences in limbic and thalamic brain volumes, on the logarithmic scale, were tested using a two-way (diagnosis and sex) univariate analysis of variance, with total cerebral volume and age controlled. RESULTS: The subjects with bipolar disorder had smaller hippocampal volumes. Further analysis revealed that this effect was driven predominantly by the female bipolar disorder subjects. In addition, both male and female youths with bipolar disorder had significantly smaller cerebral volumes. No significant hemispheric effects were seen. CONCLUSIONS: These findings support the hypothesis that the limbic system, in particular the hippocampus, may be involved in the pathophysiology of pediatric bipolar disorder. While this report may represent the largest MRI study of pediatric bipolar disorder to date, more work is needed to confirm these findings and to determine if they are unique to pediatric bipolar disorder.

Adolescent↗
PubMed2005

Dynamic statistical parametric mapping for analyzing the magnetoencephalographic epileptiform activity in patients with epilepsy.

Our current purpose is to evaluate the applicability of dynamic statistical parametric mapping, a novel method for localizing epileptiform activity recorded with magnetoencephalography in patients with epilepsy. We report four pediatric patients with focal epilepsies. Magnetoencephalographic data were collected with a 306-channel whole-head helmet-shaped sensor array. We calculated equivalent current dipoles and dynamic statistical parametric mapping movies of the interictal epileptiform discharges that were based in the minimum-L2 norm estimate, minimizing the square sum of the dipole element amplitudes. The dynamic statistical parametric mapping analysis of interictal epileptiform discharges can demonstrate the rapid change and propagation of interical epileptiform discharges. According to these findings, specific epileptogenic lesion-focal cortical dysplasia could be found and patients could be operated on successfully. The presurgical analysis of interictal epileptiform discharges using dynamic statistical parametric mapping seems to be promising in patients with a possible underlying focal cortical dysplasia and might help to guide the placement of invasive electrodes.

Adolescent↗
PubMed2005

Isolated sulfite oxidase deficiency: a case report with a novel mutation and review of the literature.

Isolated sulfite oxidase deficiency is a rare but devastating neurologic disease that usually presents in early infancy with seizures and alterations in muscle tone. Only 21 cases have been reported in the literature. We report a case of a newborn infant boy with isolated sulfite oxidase deficiency who presented with generalized seizures on his fourth day of life. Plasma total homocysteine was not detectable. Urinary sulfite, thiosulfate, and S-sulfocysteine levels were elevated. The patient began a low-methionine and low-cysteine diet and was treated with thiamine and dextromethorphan. However, he became increasingly microcephalic and was severely developmentally delayed. Mutation analysis of the sulfite oxidase gene revealed that the patient was homozygous for a novel 4-base pair deletion, and both of his parents were found to be heterozygous carriers of the same deletion. We reviewed the clinical, biochemical, neuroradiologic, and neuropathologic features in all published cases of isolated sulfite oxidase deficiency. Seizures or abnormal movements were prominent features in all cases. Developmental delays were reported in 17 cases. Ectopia lentis was detected in 9 cases. Clinical improvement with dietary therapy was seen in only 2 patients, both of whom presented after the age of 6 months and had relatively mild developmental delays. Plasma or urinary S-sulfocysteine levels were elevated in all cases. Urinary sulfite was detected in all except 1 case. Cerebral atrophy and cystic encephalomalacia were observed with neuroradiologic imaging and were noted in all 3 postmortem reports of isolated sulfite oxidase deficiency. The main alternative in the differential diagnosis of isolated sulfite oxidase deficiency is molybdenum cofactor deficiency.

Amino Acid Metabolism, Inborn Errors↗
PubMed2004

Multimodal longitudinal imaging of focal status epilepticus.

BACKGROUND: Little is understood about the evolution of structural and functional brain changes during the course of uncontrolled focal status epilepticus in humans. METHODS: We serially evaluated and treated a nine-year-old girl with refractory focal status epilepticus. Long-term EEG monitoring, MRI, MRA, SPECT, intraoperative visualization of affected cortex, and neuropathological examination of a biopsy specimen were conducted over a three year time span. Imaging changes were correlated with simultaneous treatment and EEG findings. RESULTS: The EEG monitoring showed almost continuous spike discharges emanating initially from the right frontocentral area. These EEG abnormalities were intermittently suppressed by treatment with anesthetics. Over time, additional brain areas developed epileptiform EEG abnormalities. Serial MRI studies demonstrated an evolution of changes from normal, through increased regional T2 signal to generalized atrophy. An MRA demonstrated dilatation of the middle cerebral artery stem on the right compared to the left with a broad distribution of flow-related enhancement. An 18FDG-PET scan showed a dramatically abnormal metabolic profile in the same right frontocentral areas, which modulated in response to treatment during the course of the illness. A right frontotemporal craniotomy revealed a markedly hyperemic cortical focus including vascular shunting. A sample of resected cortex showed severe gliosis and neuronal death. CONCLUSIONS: The co-registration of structural and functional imaging and its correlation with operative and pathological findings in this case illustrates the relentless progression of regional and generalized abnormalities in intractable focal status epilepticus that were only transiently modified by exhaustive therapeutic interventions. Increased flow through large vessels appeared to be shunted and did not translate into increased microvascular perfusion.

Atrophy↗
PubMed2004

Structural MR imaging.

Phased-array imaging at 1.5 and 3 T significantly improves image quality compared with that in routine 1.5-T head coil studies. These improvements significantly increase lesion detection in patients with focal epilepsy. Semiautomated image-analysis techniques have the potential to improve lesion detection, assess lesion burden more accurately, characterize cortical abnormalities, and determine the location and extent of associated cortical and deep gray nuclei involvement. With increasing interest in understanding the role white matter plays in epileptogenesis and seizure propagation, diffusion tensor imaging may yield useful information about changes in white matter organization. Our current multimodality imaging combines these structural imaging advances with coregistered neurophysiological information obtained with magnetoencephalography and with simultaneous EEG recordings. Our initial experience suggests that multimodality imaging will improve our ability to detect and define the extent of epileptogenic lesions.

Adult↗
PubMed2004

Evolution of water diffusion and anisotropy in hyperacute stroke: significant correlation between fractional anisotropy and T2.

BACKGROUND AND PURPOSE: We hypothesized that, in acute cerebral ischemic stroke, anisotropic diffusion increases if T2 signal intensity is not substantially elevated and decreases once T2 hyperintensity becomes apparent. Our purpose was to correlate fractional anisotropy (FA) measurements with the clinical time of stroke onset, apparent diffusion coefficients (ADC), and T2 signal intensity. METHODS: Tensor diffusion-weighted images (DWIs) of 25 patients were obtained within 12 hours of symptom onset. Trace DWIs, ADCs, FAs, and echo-planar T2-weighted images (T2WI) were generated. Stroke and contralateral normal volumes of interest (VOIs) were outlined on DWIs and projected onto the inherently coregistered ADC map, FA map, and echo-planar T2WI. Mean signal intensity of the ischemic and contralateral normal VOIs were compared for relatives change in ADC, FA, and signal intensity on T2WIs. RESULTS: A significant negative correlation was observed between FA and T2 signal-intensity change (r = -0.61, P =.00009). A trend of correlation between FA signal intensity and time of onset were found (r = -0.438, P =.025). No significant correlation was found between ADC and FA values (r = -0.302, P =.134). The mean ADC reduction in the ipsilateral ischemic volume was 31% +/- 11 compared with the contralateral normal side. CONCLUSION: Change in FA is inversely correlated with T2 signal intensity and, to a lesser extent, the time of onset, but it is not well correlated with ADC values in the acute stage.

Acute Disease↗
PubMed2003

Mutations in ARFGEF2 implicate vesicle trafficking in neural progenitor proliferation and migration in the human cerebral cortex.

Disruption of human neural precursor proliferation can give rise to a small brain (microcephaly), and failure of neurons to migrate properly can lead to an abnormal arrest of cerebral cortical neurons in proliferative zones near the lateral ventricles (periventricular heterotopia). Here we show that an autosomal recessive condition characterized by microcephaly and periventricular heterotopia maps to chromosome 20 and is caused by mutations in the gene ADP-ribosylation factor guanine nucleotide-exchange factor-2 (ARFGEF2). By northern-blot analysis, we found that mouse Arfgef2 mRNA levels are highest during embryonic periods of ongoing neuronal proliferation and migration, and by in situ hybridization, we found that the mRNA is widely distributed throughout the embryonic central nervous system (CNS). ARFGEF2 encodes the large (>200 kDa) brefeldin A (BFA)-inhibited GEF2 protein (BIG2), which is required for vesicle and membrane trafficking from the trans-Golgi network (TGN). Inhibition of BIG2 by BFA, or by a dominant negative ARFGEF2 cDNA, decreases cell proliferation in vitro, suggesting a cell-autonomous regulation of neural expansion. Inhibition of BIG2 also disturbed the intracellular localization of such molecules as E-cadherin and beta-catenin by preventing their transport from the Golgi apparatus to the cell surface. Our findings show that vesicle trafficking is an important regulator of proliferation and migration during human cerebral cortical development.

ADP-Ribosylation Factors↗
PubMed2003

Bilateral frontoparietal polymicrogyria: clinical and radiological features in 10 families with linkage to chromosome 16.

Polymicrogyria is a common malformation of cortical development characterized by an excessive number of small gyri and abnormal cortical lamination. Multiple syndromes of region-specific bilateral symmetric polymicrogyria have been reported. We previously have described two families with bilateral frontoparietal polymicrogyria (BFPP), an autosomal recessive syndrome that we mapped to a locus on chromosome 16q12-21. Here, we extend our observations to include 19 patients from 10 kindreds, all linked to the chromosome 16q locus, allowing us to define the clinical and radiological features of BFPP in detail. The syndrome is characterized by global developmental delay of at least moderate severity, seizures, dysconjugate gaze, and bilateral pyramidal and cerebellar signs. Magnetic resonance imaging demonstrated symmetric polymicrogyria affecting the frontoparietal regions most severely, as well as ventriculomegaly, bilateral white matter signal changes, and small brainstem and cerebellar structures. We have refined our genetic mapping and describe two apparent founder haplotypes, one of which is present in two families with BFPP and associated microcephaly. Because 11 of our patients initially were classified as having other malformations, the syndrome of BFPP appears to be more common than previously recognized and may be frequently misdiagnosed.

Adolescent↗
PubMed2003

Application of new MR techniques in pediatric patients.

Pediatric neuroradiology is a fascinating and challenging field because there are normal changes associated with normal development and unique and unusual pathologies that occur in this population. The numerous new MR techniques first applied in the adult population are appropriate for use in the pediatric population, often with minimal modification of parameters. These new techniques will undoubtedly contribute significantly to use of pediatric neuroimaging, but the adult experience is not always directly transferable. The pediatric brain, particularly the immature brain is different in structure, has predilection for different types of disease processes, and may react differently to insults than the adult brain. As a result, the role of these techniques needs to be evaluated in the context of the pediatric brain and common pediatric disease processes.

Brain↗
PubMed2003

Diffusion-weighted imaging abnormalities in the splenium after seizures.

PURPOSE: Transient increased T2 signal in the splenium of the corpus callosum after seizures has been reported and sometimes attributed to a postulated toxicity of anticonvulsant medications (AEDs). METHODS: We describe two patients with bitemporal epilepsy. RESULTS: Transiently increased T2 signal (in one) and decreased apparent diffusion coefficient (ADC) (in both) in the splenium appeared to be related directly to acute seizures. CONCLUSIONS: These cases illustrate an unusual acute postictal imaging finding, highlight involvement of an important commissural pathway, and suggest that seizures per se, and not their treatment, are the cause of transient white-matter abnormalities in these cases.

Acute Disease↗
PubMed2003

Orbital compartment syndrome mimicking cerebral herniation in a 12-yr-old boy with severe traumatic asphyxia.

OBJECTIVE: To report a case of orbital compartment syndrome mimicking cerebral herniation in a boy with severe traumatic asphyxia. DESIGN: Case report. SETTING: A tertiary-care pediatric intensive care unit. SUBJECT: A 12-yr-old boy with traumatic asphyxia syndrome. INTERVENTION: Mechanical ventilation, chest tube drainage, nitric oxide, lateral canthotomies, intracranial pressure monitoring. MEASUREMENTS AND MAIN RESULTS: A patient is presented with severe traumatic asphyxia syndrome complicated by prolonged hypoxemia, massive capillary leak syndrome, and acute onset of pupillary dilation and loss of reactivity to light. Ophthalmologic examination confirmed bilateral orbital compartment syndrome, which was treated emergently with bilateral canthotomies at the bedside. The procedure was followed by prompt return of pupillary size and function and decrease in intraocular pressure. The patient experienced complete recovery of vision in the right eye, but vision in the left eye was severely impaired. CONCLUSIONS: Our case report emphasizes the importance of considering orbital compartment syndrome in patients with traumatic asphyxia syndrome. Recognition of orbital compartment syndrome is important in this setting because prompt operative intervention may reduce the likelihood of permanent vision loss.

Accidents, Traffic↗