Lack of correlation between neuronal hyperexcitability and electrocorticographic responsiveness in epileptogenic human neocortex

1999 ◽  
Vol 90 (5) ◽  
pp. 939-945 ◽  
Author(s):  
Albert E. Telfeian ◽  
Dennis D. Spencer ◽  
Anne Williamson

Object. The purpose of this study was to determine whether intrinsic neuronal properties and synaptic responses differed between interictally active and inactive tissue removed in neocortical resections from patients undergoing surgical treatment for epilepsy.Methods. Whole-cell patch recordings were performed in layer 2 or 3 and layer 5 pyramidal cells in neocortical slices obtained from tissue surgically removed from patients for the treatment of medically intractable seizures. Synaptic responses to stimulation at the layer 6—white matter border were used to classify cells as nonbursting if they responded with only a single action potential for all above-threshold stimuli (80%). These responses were usually followed by biphasic inhibitory postsynaptic potentials (IPSPs). Cells were classified as bursting if they fired at least three action potentials in response to synaptic stimulation (20%). These cells typically showed no IPSPs and responded in either an all-or-nothing or graded fashion. Approximately twice as many cells at layer 2 or 3 (29%) than cells at layer 5 (14%) fired synaptic bursts. Synaptic bursting was not associated with an alteration in a cell's response properties to γ-aminobutyric acid. It was notable that, in tissue samples determined by electrocorticography (ECoG) to be either interictally active or not active, the proportion of cells that burst was exactly the same in both groups (24%). We found no cells with intrinsic burst firing.Conclusions. We conclude that synaptic bursting was characteristic of a small proportion of cells from epileptic tissue; however, this did not correlate with interictal spikes on ECoG.

1985 ◽  
Vol 62 (5) ◽  
pp. 750-756 ◽  
Author(s):  
Robert L. Martuza ◽  
Douglas C. Miller ◽  
David T. MacLaughlin

✓ Frozen tissue samples were obtained from meningiomas in 42 patients. Both cytosolic and nuclear fractions were tested for estradiol and progestin binding using equilibrium binding assays. The results were correlated with the age of the patient and the histological type and cellular density of the tumor. Cytosolic estradiol binding was noted in 25 (60%) of 42 tumors, with eight (19%) of the 42 having levels over 10 femtomoles (fM)/mg protein. Nuclear estradiol binding was detected in 16 (57%) of 28 tumors, with six (21%) of the 28 having levels over 10 fM/mg protein. Cytosolic progestin binding was noted in 16 (73%) of 22 samples, with levels in nine (41%) of 22 being greater than 10 fM/mg protein. There was no correlation between the level of cytoplasmic progestin binding and either the level of cytoplasmic estradiol binding or the level of nuclear estradiol binding. In several specimens, levels of cytoplasmic progestin binding in excess of 100 fM/mg protein were found in tissues demonstrating little or no estradiol binding by either the nucleus or the cytosol. This discrepancy differs from the situation found in other hormonally responsive tissues such as breast or uterus, and suggests either a possible derangement of the normal cellular hormonal control mechanism or that the measured hormone binder is a molecule other than a classical hormone receptor.


1986 ◽  
Vol 65 (2) ◽  
pp. 230-232 ◽  
Author(s):  
Peter G. Aitken ◽  
Steven J. Schiff

✓ Hippocampal tissue slices in vitro were exposed to periods of hypoxia of different durations. Addition of pentobarbital to the perfusion medium significantly increased the duration of hypoxia that was survived by CA1 pyramidal cells.


2003 ◽  
Vol 98 (4) ◽  
pp. 837-845 ◽  
Author(s):  
Lilly Tang ◽  
Mary Mantle ◽  
Paul Ferrari ◽  
Hagen Schiffbauer ◽  
Howard A. Rowley ◽  
...  

Object. The aim of this study was to evaluate the spatial accuracy of interictal magnetoencephalography (MEG) in localizing the primary epileptogenic focus in comparison with alternative MEG-derived estimates such as ictal onset recording or sensory mapping of the periphery where seizures manifest. Methods. During this retrospective study of 12 patients with epilepsy who had undergone successful magnetic source (MS) imaging with the aid of a dual 37-channel biomagnetometer as well as simultaneous MEG/electroencephalography (EEG) recordings, ictal events were observed in five patients and quantitative comparisons of interictal spike and ictal seizure onset source localizations were made. In the eight patients who had presented with sensorimotor seizure, source localization of cortical sites concordant with seizure foci was determined using somatosensory functional mapping, and the results were quantitatively compared with interictal spike source localizations. Interictal spike sources demonstrated on MEG localized to the same region as the corresponding ictal event or somatosensory source localizations. The mean distance between the ictal foci and interictal spike sources was 1.1 ± 0.3 cm. Results of functional somatosensory mapping in patients with sensorimotor seizures demonstrated that seizure sources consistently colocalized with interictal MEG spike sources, with a mean distance of 1.5 ± 0.4 cm. No systematic directional bias was observed. Interictal sources tended to be tightly clustered, and the mean ellipsoid volume, defined by one standard deviation of the source spatial coordinates, was 1 cm3. Conclusions. Interictal spike localizations on MEG were concordant with ictal and, where relevant, functional somatosensory mapping localizations. These findings support the interpretation of interictal spikes on MEG as a useful and effective noninvasive method for localizing primary seizure foci.


1986 ◽  
Vol 65 (2) ◽  
pp. 135-153 ◽  
Author(s):  
Edward G. Jones

✓ This article surveys the conventional neurotransmitters and modulatory neuropeptides that are found in the cerebral cortex and attempts to place them into the perspective of both intracortical circuitry and cortical disease. The distribution of these substances is related, where possible, to particular types of cortical neuron or to afferent or efferent fibers. Their physiological actions, where known, on cortical neurons are surveyed, and their potential roles in disease states such as the dementias, epilepsy, and stroke are assessed. Conventional transmitters that occur in afferent fibers to the cortex from brain-stem and basal forebrain sites are: serotonin, noradrenaline, dopamine, and acetylcholine. All of these except dopamine are distributed to all cortical areas: dopamine is distributed to frontal and cingulate areas only. The transmitter in thalamic afferent systems is unknown. Gamma aminobutyric acid (GABA) is the transmitter used by the majority of cortical interneurons and has a profound effect upon the shaping of receptive field properties. The vast majority of the known cortical peptides are found in GABAergic neurons, and the possibility exists that they may act as trophic substances for other neurons. Levels of certain neuropeptides decline in cases of dementia of cortical origin. Acetylcholine is the only other known transmitter of cortical neurons. It, too, is contained in neurons that also contain a neuropeptide. The transmitter(s) used by excitatory cortical interneurons and by the efferent pyramidal cells is unknown, but it may be glutamate or aspartate. It is possible that excitotoxins released in anoxic disease of the cortex may produce damage by acting on receptors for these or related transmitter agents.


2005 ◽  
Vol 102 (Special_Supplement) ◽  
pp. 56-58 ◽  
Author(s):  
István Nyáry ◽  
Otto Major ◽  
Zoltán Hanzély ◽  
György T. Szeifert

✓ Stereotactic radiosurgery is a controversial treatment modality in the management of cerebral cavernous hemangiomas (CHs), and results vary from center to center. Even the interpretation of treatment failure is controversial. It is suggested that the systematic pathological investigation of irradiated specimens could help to resolve the controversy. A hemorrhagic lesion in the posterior part of the thalamus had been diagnosed as a tumor and was treated with 40-Gy fractionated radiotherapy. One year after this treatment the case was reconsidered based on new imaging evidence, and the lesion was removed by conventional craniotomy. Histopathological examination revealed a CH with postirradiation changes. Compared with nonirradiated control CH tissue samples, there was endothelial cell destruction and marked fibrosis with scar tissue formation in the stroma of the treated lesion. The histopathological findings in this specimen were similar to those described in arteriovenous malformations after gamma knife surgery. The results of light microscopic investigations suggest that the ionizing effect of radiation energy evokes vascular and connective tissue stroma changes in CHs as well.


1972 ◽  
Vol 37 (5) ◽  
pp. 571-575 ◽  
Author(s):  
A. Loren Amacher ◽  
John M. Allcock ◽  
Charles G. Drake

✓ Fifty patients underwent 55 operations upon intracerebral angiomas; 86% had suffered intracerebral or subarachnoid hemorrhage, 8% intractable seizures, and 6% intractable headache and progressive ischemic symptoms. There was one postoperative death, a mortality rate of 2%. The operative results are considered in relation to the indications for operation and the degree of removal. The importance of postoperative angiography is stressed.


1985 ◽  
Vol 63 (6) ◽  
pp. 944-948 ◽  
Author(s):  
Michael M. Todd ◽  
Concezione Tommasino ◽  
Suzanne Moore

✓ In view of a growing interest in the resuscitative use of hypertonic saline solutions, the authors have examined the cerebral effects of isovolemic hemodilution carried out over 1 hour (hematocrit decreased from 40% to 20%, stable arterial and right arterial pressures), using a hypertonic lactated Ringer's solution (HT-LR:Na+ 252 mEq/liter, osmolality 480 mOsm/liter). Experiments were carried out in anesthetized ventilated rabbits. Measured variables included cerebral blood flow (using the H2 clearance method), intracranial pressure (ICP), the electroencephalogram, spinal cord and skeletal muscle water content (%H2O), and the specific gravity of small (10- to 30-mg) tissue samples taken from different areas of the left hemisphere (including the cortex, thalamus, internal capsule, and hippocampus). The changes produced by HT-LR were compared with those seen in both undiluted control animals and in rabbits hemodiluted with normal saline (Na+ 155 mEq/liter, osmolality 310 mOsm/liter). The results demonstrate that hemodilution with HT-LR leads to the expected increases in serum Na+ and osmolality (158 ± 6 mEq/liter and 320 ± 5 mOsm/kg, respectively, mean ± standard deviation) and that these were accompanied by reductions in the %H2O of all cerebral and extracerebral tissues, increases in the specific gravity of all tissue regions studied, and a decrease in ICP (1.9 ± 0.7 mm Hg). By contrast, rabbits with hemodilution by normal saline showed no changes in either %H2O or specific gravity, but had significant increases in ICP (3.3 ± 1.3 mm Hg). Cerebral blood flow increased in all animals hemodiluted with either HT-LR or normal saline by a combined average of +29 ml/100 gm/min. Although these studies were performed in neurologically normal animals, the combination of cerebral changes seen with HT-LR (cerebral dehydration, less peripheral edema, decreased ICP but with increased cerebral blood flow) suggests that this approach may have some advantages over the use of isotonic fluids, and may have some utility in the resuscitation of head-injured patients.


2001 ◽  
Vol 95 (5) ◽  
pp. 839-844 ◽  
Author(s):  
Ann-Christin Sandberg Nordqvist ◽  
Hubert Smurawa ◽  
Tiit Mathiesen

Object. Meningiomas display clinical characteristics that vary from very benign to clearly malignant with rapid invasive growth and metastasis. Benign meningiomas differ in their invasiveness and concomitant edema. This study was undertaken to analyze the expression of matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9, respectively) in meningiomas associated with different degrees of brain invasion and edema. Methods. Tissue samples from 16 meningiomas were selected according to tumor invasiveness from a consecutive series of patients. Samples were analyzed for expression of both MMP-2 and MMP-9 by using in situ hybridization. The meningiomas consisted of three types: Group I, benign meningiomas that did not interfere with the arachnoid plane and exhibited no edema; Group II, benign meningiomas that invaded the arachnoid plane and caused edema; and Group III, aggressive and malignant meningiomas that caused edema and displayed brain invasion. In all 16 tumors analyzed, MMP-2 mRNA was identified. Levels of expression of MMP-2 mRNA were similar in all samples, and no correlation with increasing tumor invasiveness or associated edema could be detected. Expression of MMP-9 mRNA was identified in 14 of the 16 tumors, and a clear correlation with increasing tumor invasion into the brain was noted. Conclusions. Meningiomas express both MMP-2 and MMP-9. Tumor invasiveness, which ranged from minor with respect to the arachnoid membrane and progressed to frank brain invasion, correlated with the extent of MMP-9 expression. The findings indicate that MMP-9 expression and brain invasion are relevant mechanisms that must be interfered with in the treatment of aggressive and malignant meningiomas. No such correlation with MMP-2 was found.


1995 ◽  
Vol 83 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Itzhak Fried ◽  
Dennis D. Spencer ◽  
Susan S. Spencer

✓ An aura is generally understood to be the beginning of a seizure. Yet, following successful surgery for intractable epilepsy, patients may have persistent auras even though they are otherwise seizure free. Ninety patients with intractable seizures and auras underwent resective surgery. Forty-three patients had hippocampal sclerosis and 47 had temporal or extratemporal lesions such as glial tumors or vascular malformations. The semiology of the auras was found to have value in localization but not lateralization of the pathology. Epigastric auras as well as gustatory and olfactory auras were significantly more frequent in patients with hippocampal sclerosis than in those with temporal or extratemporal lesions. Auras of vertigo or dizziness were most frequent in patients with extratemporal pathology. There was a significant difference between the pathology groups in the efficacy of resection in eliminating the auras. Of the patients with hippocampal sclerosis who were rendered seizure free, 18.9% had persistent auras, whereas only one (2.6%) of the patients with temporal or extratemporal lesions who were rendered seizure free had persistent auras. These findings suggest that for patients with hippocampal sclerosis an anatomical dissociation between seizure and aura may occur, whereas this dissociation is not present in patients with lesions. Patients suspected of having hippocampal sclerosis should be counseled preoperatively as to the significant likelihood of persistent auras even if seizures are successfully abolished.


1998 ◽  
Vol 89 (3) ◽  
pp. 431-440 ◽  
Author(s):  
Gerard Bruno ◽  
Roxanne Todor ◽  
Isabel Lewis ◽  
Douglas Chyatte

Object. The occurrence of cerebral aneurysms has been linked to alterations in the extracellular matrix and to matrix-degrading proteases. The purpose of the present study was to determine whether active extracellular matrix remodeling occurs within cerebral aneurysms. Methods. Aneurysm tissue was collected from 23 patients (two of whom had a ruptured aneurysm and 21 of whom had an unruptured aneurysm) and compared with 11 control basilar arteries harvested at autopsy. Active proteinases capable of gelatin lysis were identified by performing in situ zymography in the presence and absence of a metalloproteinase inhibitor (ethylenediamine tetraacetic acid) and a serine proteinase inhibitor (phenylmethylsulfonyl fluoride). Immunohistochemical analysis was used to localize plasmin, tissue-type (t)—plasminogen activator (PA), urokinase-type (u)—PA, membranetype (MT1)—matrix metalloproteinase (MMP), MMP-2, MMP-9, and tenascin. Focal areas of gelatin lysis occurred in most cerebral aneurysm tissue samples (17 of 21), but rarely in control arteries (two of 11) (p = 0.002). Both serine proteinases and MMPs contributed to gelatin lysis; however, the MMPs were the predominant enzyme family. Plasmin (p = 0.04) and MT1-MMP (p = 0.04) were expressed in the aneurysm tissue but were unusual in control tissue. The MMP-2 was also expressed more commonly in aneurysm than in control tissue (p = 0.07). The MMP-9 and t-PA were expressed in both groups; however, different staining patterns were observed between aneurysm and control tissue. Tenascin staining was commonly present in both groups, whereas u-PA staining was rarely present. Conclusions. Aneurysm tissue demonstrates increased proteolytic activity capable of lysing gelatin and increased expression of plasmin, MT1-MMP, and MMP-2 when compared with normal cerebral arteries. This activity may contribute to focal degradation of the vascular extracellular matrix and may be related to aneurysm formation and growth.


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