Epileptic Brain Tissue Research Articles

Advances in neuroimaging: non-substrate-directed partial epilepsy.

Contemporary neuroimaging studies using structural and functional techniques are critical in the evaluation of patients with localization-related epilepsy. Imaging procedures may be used to localize the epileptic brain tissue or determine the likely pathologic findings underlying the epileptogenic zone, or both. The diagnostic yield of magnetic resonance imaging (MRI) has been demonstrated in patients with partial epilepsy. The identification of an MRI epileptogenic lesion is almost invariably a reliable indicator of the site of seizure onset. Peri-ictal single photon emission computed tomography (SPECT) may be of particular benefit in patients with normal MRI studies. The use of neuroimaging in the care and management of patients with partial epilepsy is discussed here.

GABAergic mechanisms in epilepsy.

gamma-Aminobutyric acid (GABA), the principal inhibitory neurotransmitter in the cerebral cortex, maintains the inhibitory tone that counterbalances neuronal excitation. When this balance is perturbed, seizures may ensue. GABA is formed within GABAergic axon terminals and released into the synapse, where it acts at one of two types of receptor: GABAA, which controls chloride entry into the cell, and GABAB, which increases potassium conductance, decreases calcium entry, and inhibits the presynaptic release of other transmitters. GABAA-receptor binding influences the early portion of the GABA-mediated inhibitory postsynaptic potential, whereas GABAB binding influences the late portion. GABA is rapidly removed by uptake into both glia and presynaptic nerve terminals and then catabolized by GABA transaminase. Experimental and clinical study evidence indicates that GABA has an important role in the mechanism and treatment of epilepsy: (a) Abnormalities of GABAergic function have been observed in genetic and acquired animal models of epilepsy; (b) Reductions of GABA-mediated inhibition, activity of glutamate decarboxylase, binding to GABAA and benzodiazepine sites, GABA in cerebrospinal fluid and brain tissue, and GABA detected during microdialysis studies have been reported in studies of human epileptic brain tissue; (c) GABA agonists suppress seizures, and GABA antagonists produce seizures; (d) Drugs that inhibit GABA synthesis cause seizures; and (e) Benzodiazepines and barbiturates work by enhancing GABA-mediated inhibition. Finally, drugs that increase synaptic GABA are potent anticonvulsants. Two recently developed antiepileptic drugs (AEDs), vigabatrin (VGB) and tiagabine (TGB), are examples of such agents. However, their mechanisms of action are quite different (VGB is an irreversible suicide inhibitor of GABA transaminase, whereas TGB blocks GABA reuptake into neurons and glia), which may account for observed differences in drug side-effect profile.

Extracellular amino acid levels measured with intracerebral microdialysis in the model of posttraumatic epilepsy induced by intracortical iron injection

An iron induced model of posttraumatic chronic focal epilepsy in rats was studied with respect to extracellular amino acids, electrophysiology, and morphology, approx. 6 months after intracortical injection of ferrous chloride. Twenty-six of the twenty-eight (93%) rats developed spontaneous epileptiform EEG-activity and electrical cortical stimulation done in eight animals evoked seizure activity in five animals (62.5%). Epileptic brain tissue displayed significantly higher extracellular interictal levels of aspartate (ASP), compared to normal brain, measured with intracerebral microdialysis. The interictal levels of serine (SER) were significantly higher at the lesion side compared to the contralateral cortex in epileptic animals. Spontaneous elevations of ASP and glutamate (GLU) levels up to 8 times the basal level were found in 4/5 (80%). There was no consistent amino acid pattern following the electrically induced seizures, but in association with more intense seizure activity ASP and GLU were elevated. Histopathologically, the necrotic lesions in the cortex contained small vessels and iron pigment loaded astrocytes. Scattered eosinophilic neurons were found in the hippocampus, bilaterally in 37% of the animals. The results show that a focal epileptiform activity developed in a high percentage of animals that received an intracortical iron injection. The observed amino acid changes in epileptic animals may be involved in the development of seizures in this model of posttraumatic epilepsy.

NMDA-Receptor Activity in Epileptic Brain Tissue Visualized by (S)-[N-methyl-11C]Ketamine

NMDA-Receptor Activity in Epileptic Brain Tissue Visualized by (S)-[N-methyl-11C]Ketamine

Surgical treatment for perirolandic lesional epilepsy.

Our purpose was to evaluate the safety and efficacy of surgical treatment for perirolandic lesional epilepsy. We analyzed the records of 14 consecutive patients who underwent a stereotactic lesionectomy for intractable partial epilepsy between 1985 and 1994. All patients had a neuroimaging-identified lesion in the perirolandic cortex. The mean duration of follow-up was 6 years (range 1-11 years). Thirteen patients (93%) had a significant improvement in seizure tendency. Eleven patients (78%) were rendered seizure-free. Morbidity occurred in only one patient, who experienced an increased monoparesis after surgery. Stereotactic lesionectomy is an effective surgical strategy in patients with perirolandic lesional epilepsy. The recent development of functional brain imaging using subtraction ictal single-photon emission computed tomography co-registered with volumetric magnetic resonance imaging has been shown to be a reliable indicator of epileptic brain tissue that may significantly alter the preoperative evaluation in patients with extratemporal seizures.

Classification of 1H MR spectra of human brain neoplasms: the influence of preprocessing and computerized consensus diagnosis on classification accuracy.

We study how classification accuracy can be improved when both different data preprocessing methods and computerized consensus diagnosis (CCD) are applied to 1H magnetic resonance (MR) spectra of astrocytomas, meningiomas, and epileptic brain tissue. The MR spectra (360 MHz, 37 degrees C) of tissue specimens (biopsies) from subjects with meningiomas (95; 26 cases), astrocytomas (74; 26 cases), and epilepsy (37; 8 cases) were preprocessed by several methods. Each data set was partitioned into training and validation sets. Robust classification was carried out via linear discriminant analysis (LDA), artificial neural nets (NN), and CCD, and the results were compared with histopathological diagnosis of the MR specimens. Normalization of the relevant spectral regions affects classification accuracy significantly. The spectra-based average three-class classification accuracies of LDA and NN increased from 81.7% (unnormalized data sets) to 89.9% (normalized). CCD increased the classification accuracy of the normalized sets to an average of 91.8%. CCD invariably decreases the fraction of unclassifiable spectra. The same trends prevail, with improved results, for case-based classification. Preprocessing the 1H MR spectra is essential for accurate and reliable classification of astrocytomas, meningiomas, and nontumorous epileptic brain tissue. CCD improves classification accuracy, with an attendant decrease in the fraction of unclassifiable spectra or cases.

Extratemporal cortical resections and lesionectomies for partial epilepsy: complications of surgical treatment.

Fifty patients with medically refractory extratemporal seizures underwent epilepsy surgery at our institution between 1988 and 1992. Twenty-nine patients (group I) had an extratemporal (mainly frontal lobe) corticectomy, and 21 patients (group II) had an epileptogenic lesion extirpated without resection of the epileptic brain tissue. Comprehensive neurologic evaluation was performed preoperatively, soon after operation, and approximately 3 months postoperatively to assess operative outcome. Magnetic resonance imaging (MRI) in group I patients usually showed no abnormality or a large destructive lesion. Neuroimaging showed a foreign tissue lesion in most group II patients. Thirteen of the 29 patients who underwent corticectomy had at least one adverse event (AE) potentially related to operation at the time of initial assessment. Four of the 13 patients required a surgical procedure to treat the operative complication, but only 1 of the 13 patients had a persistent neurologic deficit at follow-up examination. Three of the 21 patients who received lesionectomy had acute and persistent neurologic morbidity. Patients undergoing cortical resection remained intubated longer postoperatively (p < 0.005), and required longer hospitalization after operation (p < 0.001) and in the intensive care unit (p < 0.001) as compared with the lesionectomy group. Results of this study may prove useful in counseling patients regarding neurologic outcome after extratemporal surgery.

Magnetic-resonance-imaging-based volume studies in patients with bitemporal epileptiform abnormalities

We performed a prospective study of magnetic resonance imaging (MRI) based hippocampal formation (HF) volumetry in 10 patients with intractable partial epilepsy of anterior temporal lobe origin. Extracranial ictal EEG recordings did not allow appropriate localization of the epileptogenic zone, and all patients required depth EEG. Chronic intracranial monitoring revealed the anterior temporal lobe onset of seizures in all patients. MRI showed a lateralized hippocampal alteration, i.e., HF atrophy and/or an increased T2-signal intensity, in 5 of the 10 patients that correctly identified the epileptic temporal lobe. Quantitative HF atrophy coexisted with the site of seizure onset as determined by the intracranial EEG recordings in four patients. Volumetry was indeterminant for atrophy in six patients. An increased mesial temporal T2-signal intensity in one patient correlated with the temporal lobe of seizure origin. MRI-identified hippocampal pathology may be highly specific in patients with bitemporal epileptiform abnormalities to indicate the localization of epileptic brain tissue.

Quinolinic-phosphoribosyl transferase activity is decreased in epileptic human brain tissue.

The presence of the excitotoxic and convulsant agent quinolinic acid (QUIN) in human brain has led to the hypothesis that an increase of this tryptophan metabolite could serve as an endogenous epileptogen. A possible mechanism for a pathological accumulation of QUIN being a deficiency in its degradation, we have measured the activity of quinolinic-phosphoribosyl transferase (QPRTase) (its first degradative enzyme) in stereo-EEG identified biopsies of human brain tissue. A specific reduction of QPRTase activity was observed in tissue primarily involved in the epileptic discharge compared to values from postmortem human brain tissue with no neurological disorders or nonpathological tissue from epileptic brains. A more severe decrease was noticed in the frontal and temporal cortices as compared to the amygdala or Ammon's horn. We suggest that this local deficit may contribute to the establishment or maintenance of an epileptic focus.

Epileptic PET Probes

R yan Peterson is living proof that half a brain can be better than a whole brain. Ryan was only 8 hours old when his body began to convulse from his first brain seizure. Over the next few months doctors gave him a variety of anticonvulsant drugs, but his tiny brain continued to churn out seizures at the rate of 15 to 20 per day. If internal electrical storm continued, he, like other infants with uncontrollable epilepsy, would probably die of seizure-related complications by age 10. Faced with this prospect, Ryans parents brought him to the University of California at Los Angeles School of Medicine, where a team of physicians directed by neurologist Harry T. Chugani searched for the source of the seizures. With the crucial help of positron emission tomography (PET) images of brain, they mapped abnormal activity underlying the seizures throughout nearly all of his left hemisphere. At age 15 months, neurosurgeons removed the extensive mass of seizurecausing tissue. Now approaching his fourth birthday, Ryan is beginning to talk and take his first steps. His development is slower than that of children born with healthy brains, but his seizures are under control. Chugani expects his intellectual abilities to unfold with few or no hitches. There may be, however, some weakness on the right side of his body, which normally is regulated by the left hemisphere. Ryan's mother says it's almost as if he were born at the time of the surgery, notes Chugani. This and similar cases have shed light on the remarkable recovery powers of the young brain, while at the same time pioneering an important new avenue for PET imaging as a tool for examining infants with uncontrollable epilepsy. Much of this newfound ability can be traced to recent advances in resolution of PET images. In an upcoming issue of NEUROLOGY, Chugani and his colleagues report that PET data, combined with more traditional measures such as electroencephalographic (EEG) recording of brain electrical activity, greatly increased the ability to distinguish between epileptic and healthy brain tissue in eight such youngsters, including Ryan, ranging in age from 18 days to 5 years. Six of the children had epileptic tissue confined to one side of the brain, making them good candidates for surgery. PET has a bright future both as a diagnostic tool for identifying diseased parts of the brain and as a surveyor of normal brain functions, says Chugani. He and his co-workers have already used this technology to chart a tremendous burst of brain activity occurring only during childhood, which may be related to the considerable learning and recuperative powers of the young brain.

Restriction of the spread of epileptic discharges in cats by means of Bragg peak, intracranial irradiation

Adult male cats with a single epileptic focus receive neon ion Bragg peak radiation at the Bevalac at Lawrence Berkeley Laboratory. Bragg peak radiation is doposited in a thin disc of brain tissue beneath an epileptogenic focus produced with alumina cream. Paroxysmal electroencephalograms (EEGs) from the occipital cortex of cats confirm the bioelectric changes in the pathogenesis of epilepsy. Distant spread of seizure activity occurs when the cells in the cortical focus fire a series of relatively simultaneous spikes at high frequency with sufficient intensity to develop self-sustained discharges in remote brain areas. The development of a “mirror focus” in the EEG records in the contralateral cortex gives a measure of the distances paroxysmal discharges spread. Interhemispheric responses (IHR) that travel from the alumina-treated cortex via the corpus callosum to the contralateral cortex are a second measure of pathways over which paroxysmal discharges spread. In cat studies Bragg peak radiation is positioned beneath the epileptic cortical focus. Various heavy ion doses are employed to test whether an absorbed dose per cat is sufficient to block the transmission of epileptic activity as a function of the post-irradiation time. The relationship between neon ion dose and the post-irradiation time for the loss of IHR is a measure of the physiological dissociation of the epileptic brain tissue from the remainder of the brain. The loss of the “mirror focus” in EEG records agrees with the IHR findings.