Search PubMed⌕ Search

Biomedical subjects

Andrew J Cole

Publications and source records attributed to Andrew J Cole.

16 recordsLinked to original sources
PubMed2006

Efficacy of surgical treatment of de novo, adult-onset, cryptogenic, refractory focal status epilepticus.

BACKGROUND: There have been few published reports of successful surgical treatment of focal status epilepticus. Surgical intervention is considered a last resort after medical strategies have been exhausted. OBJECTIVE: To report a case of an adult who was initially seen with de novo, medically refractory, cryptogenic focal status epilepticus and underwent resection of an electrographically defined portion of the left middle frontal gyrus with multiple subpial transections of the adjacent cortex resulting in termination of the electroclinical seizure activity. DESIGN: Report of a case of successful surgical treatment of cryptogenic focal status epilepticus. INTERVENTION: After an initial 35 days of oral antiepileptic drug therapy and subsequent 16 days of continuous electroencephalography-guided intravenous antiepileptic drug therapy in an intensive care unit setting, and after extensive preoperative and intraoperative characterization of the epileptogenic zone, a tailored resection of the left middle frontal gyrus with multiple subpial transections of the surrounding cortex was performed. RESULTS: The restricted surgical resection and multiple subpial transections terminated the seizure activity. Neuropathological examination of the resected tissue revealed moderate inflammatory changes and a few abnormally located neurons without any definitive evidence of dysplasia, which was suspected preoperatively. CONCLUSIONS: We suggest that focal cortical resection may be an appropriate intervention in medically refractory focal status epilepticus even when an overt structural etiology is not evident preoperatively and should be considered as an option at the onset of intractability.

Adult↗
PubMed2005

Susceptibility to seizure-induced injury and acquired microencephaly following intraventricular injection of saporin-conjugated 192 IgG in developing rat brain.

To study the role of neurotrophin-responsive neurons in brain growth and developmental resistance to seizure-induced injury, we infused saporin-conjugated 192-IgG (192 IgG-saporin), a monoclonal antibody directed at the P75 neurotrophin receptors (p75(NTR)), into the ventricles of postnatal day 8 (P8) rat pups. 7-10 days after immunotoxin treatment, loss of p75(NTR) immunoreactivity was associated with depletion of basal forebrain cholinergic projection to the neocortex and hippocampus. Kainic acid (KA)-induced seizures on P15 resulted in hippocampal neuronal injury in the majority of toxin-treated animals (13/16), but only rarely in saline-injected controls (2/25) (P < 0.001). In addition, widespread cerebral atrophy and a significant decrease in brain weight with preserved body weight were observed. Volumetric analysis of the hippocampal hilar region revealed a 2-fold reduction in perikaryal size and a 1.7-fold increase in cell packing density after 192 IgG-saporin injection. These observations indicate that neurotrophin-responsive neurons including basal forebrain magnocellular cholinergic neurons may be critical for normal brain growth and play a protective role in preventing excitotoxic neuronal injury during development.

Animals↗
PubMed2005

Hyperacute neuropathological findings after proton beam radiosurgery of the rat hippocampus.

OBJECTIVE: To study the hyperacute histological and immunohistochemical effects of stereotactic proton beam irradiation of the rat hippocampus. METHODS: Nine rats underwent proton beam radiosurgery of one hippocampus with nominal doses of cobalt-2, -12, and -60 Gray equivalents (n = 3 each). Control animals (n = 3) were not irradiated. Animals were killed 5 hours after irradiation and brain sections were stained for Nissl, silver degeneration, deoxyribonucleic acid (DNA) fragmentation (DNAF), and the activated form of two mitogen-activated protein kinases (MAPKs), phospho-Erk1/2 (P-Erk1/2) and p38. Stained cells in the hippocampus expressing DNAF and/or P-Erk1/2 were counted. Confocal microscopy with double immunofluorescent staining was used to examine cellular colocalization of DNAF and P-Erk1/2. RESULTS: Both DNAF and P-Erk1/2 showed quantitative dose-dependent increases in staining in the targeted hippocampus compared with the contralateral side and controls. This finding was restricted to the subgranular proliferative zone of the hippocampus. Both markers also were up-regulated on the contralateral side when compared with controls in a dose-dependent fashion. Simultaneous staining for DNAF and P-Erk1/2 was found in fewer than half of all cells. p38 was unchanged compared with controls. Although Nissl staining appeared normal, silver stain confirmed dose-dependent cellular degeneration. CONCLUSION: DNAF, a marker of cell death, was present in rat hippocampi within 5 hours of delivery of cobalt-2 Gray equivalents stereotactically focused irradiation, suggesting that even low-dose radiosurgery has hyperacute neurotoxic effects. Activated mitogen-activated protein kinase was incompletely colocalized with DNAF, suggesting that activation of this cascade is neither necessary nor sufficient to initiate acute cell death after irradiation.

Animals↗
PubMed2004

MRI changes in the rat hippocampus following proton radiosurgery.

PURPOSE: To define radiographic dose-response relationships for proton radiosurgery using a rat brain model. METHODS AND MATERIALS: A group of 23 rats was treated with Bragg peak proton beam irradiation involving the right hippocampus. Single doses of 5, 12, 20, 30, 60, 90 and 130 cobalt gray equivalents (CGE) were delivered to groups of 3 animals using single fraction technique. One extra animal was included at the 130- and 30-CGE doses. Animals were imaged using a standard 1.5-tesla GE Signa MRI. A 3-inch surface coil was employed to obtain T1-weighted sagittal images (TR 600 and TE 30) and dual echo T2-weighted coronal images (TR 3,000 and TE 30/90). Animals were imaged at 1.5, 3, 4.5, 6 and 9 months. Volumetric analysis with custom software was done to evaluate areas of increased signal on T2-weighted images, and signal change versus time curves were generated. Gadolinium-enhanced T1-weighted imaging was also done at the 9-month time point to further evaluate tissue injury. The development of hydrocephalus was also examined. RESULTS: Peak tissue injury was greater and occurred earlier with higher versus lower doses of radiation. Statistically significant differences were seen between the 130- and 90-CGE animals and between the 90- and 60-CGE animals (p < 0.0016) using ANOVA. Signal changes can be seen in at least 1 of the animals at 20 CGE. The largest volume of tissue enhancement at 9 months was seen in animals at 60 CGE, which may represent an intermediate zone of tissue injury and gliosis compared with greater tissue loss at higher doses and less injury at lower doses. Hydrocephalus developed first in the untreated hemisphere in 130- and 90-CGE animals as a result of mass effect while it occurred at a later time in the treated hemisphere in lower-dose animals. CONCLUSIONS: Following single-dose proton radiosurgery of rat hippocampus, serial MRIs show T2 signal changes in animals ranging from 130 down to 20 CGE as well as the development of hydrocephalus. Dose-effect relationships using proton radiosurgery in rats will be a helpful step in guiding further studies on radiation injury to brain tissue.

Animals↗
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

Status epilepticus and periictal imaging.

Peri- and postictal changes on both anatomic and functional imaging examinations have been recognized for many years. With the wide availability of magnetic resonance imaging and positron emission tomography, a growing range of recognized acute imaging findings have been described. Periictal and postictal findings can be classified as either local or remote, with respect to the site of maximal ictal EEG abnormality. Although many of the findings described are reversible, the factors that determine whether findings will resolve are incompletely understood. This article considers the range of findings that have been described, places them into the context of known or hypothesized pathophysiologic mechanisms, and considers their clinical significance. A framework is proposed for considering the relation between ictal duration and severity, the characteristics of imaging abnormalities, and the mechanism of their underlying pathophysiology.

Adult↗
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

Radiosurgery of the rat hippocampus: magnetic resonance imaging, neurophysiological, histological, and behavioral studies.

OBJECTIVE: To explore the histological, electrophysiological, radiological, and behavioral effects of radiosurgery using a new model of proton beam radiosurgery (PBR) of the rodent hippocampus. METHODS: Forty-one rats underwent PBR of the right hippocampus with nominal doses of 5 to 130 cobalt Gray equivalents (CGE). Three control animals were untreated. Three months after PBR, 41 animals were evaluated with the Morris water maze, 23 with T2-weighted magnetic resonance imaging, and 22 with intrahippocampal microelectrode recordings. Animals that were studied physiologically were killed, and their brains were examined with Nissl staining and immunocytochemical staining for glutamic acid decarboxylase, heat shock protein 72 (HSP-72), parvalbumin, calmodulin, calretinin, calbindin, and somatostatin. RESULTS: Ninety and 130 CGE resulted in decreased performance in the Morris water maze, increased signal on T2-weighted magnetic resonance imaging, diminished granule cell field potentials, and tissue necrosis, which was restricted to the irradiated side. These doses also resulted in ipsilateral up-regulation of calbindin and HSP-72. Parvalbumin was down-regulated at 130 CGE. The 30 and 60 CGE animals displayed a marked increase in HSP-72 staining on the irradiated side but no demonstrable cell loss. No asymmetries were noted in somatostatin, calretinin, and glutamic acid decarboxylase staining. Normal physiology was found in rats receiving up to 60 CGE. CONCLUSION: This study expands our understanding of the effects of radiosurgery on the mammalian brain. Three months after PBR, the irradiated rat hippocampus demonstrates necrosis at 90 CGE, but not at 60 CGE, with associated abnormalities in magnetic resonance imaging, physiology, and memory testing. HSP-72 was up-regulated at nonnecrotic doses.

Animals↗
PubMed2002

Phosphorylation of P42/P44 MAP kinase and DNA fragmentation in the rat perforant pathway stimulation model of limbic epilepsy.

The intracellular signaling pathways associated with neuronal injury after perforant pathway stimulation of the rodent hippocampus have not been examined. To determine whether activation of the p42/p44 (Erk1/2) MAP kinase (MAPK) phosphorylation cascade is linked to neuronal injury after perforant pathway stimulation (PPS), we stained for phosphorylated Erk1/2 (P-Erk1/2) and for DNA fragmentation, a marker of cell death after PPS. Eighteen Sprague-Dawley rats underwent PPS for 6 (n=6), 12 (n=6), or 24 (n=6) h and were sacrificed either immediately (n=9) or 48 h (n=9) after stimulation. Sham-operated non-stimulated control animals (n=2) and control animals receiving low frequency stimulation only (n=4) were also examined. Brain sections were stained for DNA fragmentation and P-Erk1/2. DNA fragmentation was evident only in granule cells and CA3 pyramidal cells of the stimulated side 48 h after 24 h of PPS. PPS resulted in robust phosphorylation of Erk1/2 that displayed a stereotyped timecourse, appearing first in hilar neurons on the ipsilateral side and later in hilar neurons, granule cells, hippocampal pyramidal and non-neuronal cell populations on both the stimulated and contralateral sides. Both Erk1/2 phosphorylation and DNA fragmentation show definite and reproducible staining patterns after PPS that vary based on duration of stimulation. Populations displaying Erk1/2 activation appeared to differ from those showing DNA fragmentation and neuronal injury.

Animals↗
PubMed2002

Are seizures harmful: what can we learn from animal models?

Epilepsy is a brain disease that requires distributed neuronal networks for its expression. Several characteristics of epilepsy, including its natural history, the latency between an initial insult and the first manifestation of seizures, the complex interaction of seizures with development as a function of developmental stage, the modulating effect of systemic physiological responses, and the fact that seizures are ultimately defined by a combination of electrical and behavioral criteria all suggest that epilepsy should ideally be studied in an intact whole animal preparation. Such preparations offer the ability to study acute and chronic changes in brain structure and function after single or repeated seizures. Animal models have major limitations, however, including strain specificity, difficulty in isolating potentially confounding variables, a relative lack of accessible higher cortical functions, such as language and abstract processing, and shorter lifespans that may be insufficient to allow the complete expression of seizure-related injury. Information we have learned from animal studies includes a broad understanding of the chemical, molecular and anatomic consequences of seizures, including their temporal and spatial relationships to each other, and information on the consequences of seizures as a function of development. Recent studies have cast light on potential mechanisms of resistance to seizure-induced injury in the developing brain. In the future, we can anticipate that animal models will continue to be useful, especially when whole-animal preparations are used to generate material for detailed in vitro examination.

Animals↗