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Objectives: To investigate the use of whole brain voxel based morphometry (VBM) and stereological analysis to study brain morphology in patients with medically intractable temporal lobe epilepsy; and to determine [...]

Mossy cells are bi-directionally connected through a positive feedback loop to granule cells, the principal cells of the dentate gyrus. This recurrent circuit is strategically placed between the entorhinal cortex and the hippocampal CA3 region. In spite of their potentially pro-convulsive arrangement with granule cells, mossy cells have not been seriously considered to promote seizures, because mossy cells, allegedly one of the most vulnerable cell types in the entire mammalian brain, have long been `known' to die en masse in epilepsy. However, new data suggest that rumors of the rapid demise of the mossy cells might have been greatly exaggerated.

Abstract The objective was to assess the changes in cortical excitability after sleep deprivation in normal subjects. Sleep deprivation activates EEG epileptiform activity in an unknown way. Transcranial magnetic stimulation [...]

Chronically epileptic (induced by a single systemic injection of lithium and pilocarpine about 30 days before the experiment began) male rats were trained within a radial maze while they were administered either GABA-pentin (Neurontin), or prednisolone or given no treatment. There was no significant improvement in learning or memory between the groups. Numbers of trials per day were positively correlated with the time required to display the overt stereotyped forelimb clonus after the single pilocarpine injection. The numbers of correct trials completed during the first few days of acquisition were significantly greater for the rats that had received weak (1 [Mu]T) complex, pulsed magnetic fields over the right hemisphere during the first 24 hr. after seizure induction than for those who received the same field over the left hemisphere or that had been exposed to reference conditions. Implications of the enhanced sensitivity of limbic neurons to subtle electromagnetic interaction during electrical lability are discussed.

The occurrence of physiological cell death has been known for decades, but interest in the subject was renewed in 1972 when Kerr, Wyllie and Currie described in detail the ultrastructural changes characteristic of dying cells and coined the term apoptosis to describe the process. Cells display a wide variety of morphological changes when dying during development or following a toxic insult. A binary classification scheme suggests that physiologically appropriate death is due to apoptosis and that pathological mechanisms involve necrosis. However, recent studies indicate a potential involvement of apoptotic cell death in ischemia, status epilepticus and HIV-I infection.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/S0166-2236(96)80039-7 Byline: C. Charriaut-Marlangue, D. Aggoun-Zouaoui, A. Represa, Y. Ben-Ari Abstract: The occurrence of physiological cell death has been known for decades, but interest in the subject was renewed in 1972 when Kerr, Wyllie and Currie described in detail the ultrastructural changes characteristic of dying cells and coined the term apoptosis to describe the process. Cells display a wide variety of morphological changes when dying during development or following a toxic insult. A binary classification scheme suggests that physiologically appropriate death is due to apoptosis and that pathological mechanisms involve necrosis. However, recent studies indicate a potential involvement of apoptotic cell death in ischemia, status epilepticus and HIV-I infection.

I. INTRODUCTION The issue of how neurons communicate fueled an intense debate during the decades around the turn of the [TABULAR DATA FOR TABLE 1 OMITTED] century. Controversy centered on [...]

Byline: Nedim. Durmus, Sefa. Gültürk, Tijen. Kaya, Tuncer. Demir, Mesut. Parlak, Ahmet. Altun Objectives: It is suggested that excessive calcium entry into neurons is the main triggering event in the [...]

Many patients with epilepsy have abnormal patterns of brain electrical activity that are present even when seizures are not occurring. (The electrical activity is measured by electroencephalography or EEG.) These interictal epileptiform discharges, or IEDs, are present on both sides of the brain in 20 to 35 percent of patients with temporal lobe epilepsy. Curiously, the precise sources of the abnormal activity, or foci, are often symmetric. It might be anticipated that this bitemporal activity is more common in patients whose epilepsy has resulted from causes that are more global in nature. For example, the effects of a high fever affect all parts of the brain and might therefore be more likely to cause bitemporal epilepsy than, say, a brain tumor which exerts its effect in a limited region on one side of the brain. Researchers set out to confirm this hypothesis by comparing the case records of 30 patients with unitemporal IEDs with those of 30 patients with bitemporal IEDs. The researchers did not anticipate finding the exact opposite to be the case. Seizures resulting from fever were actually more common among the patients with the unitemporal foci (40 percent) than with the bitemporal foci (17 percent). Conversely, 7 of the 10 patients with tumor masses had bitemporal rather than unitemporal IEDs. This suggests that the occurrence of epileptic foci in both temporal lobes of the brain is not more likely to have resulted from fever or infection, pathologic conditions with effects spanning the brain. These results hint that the bitemporal foci may actually result from secondary epileptogenesis. This pathologic process, which has been demonstrated in animals but remains unconfirmed in human patients, occurs when the initial epileptic focus in one area stimulates the formation of new epileptic foci elsewhere. These new foci did not result directly from the original cause, hence the name secondary. This process would provide an explanation for the symmetry that is often seen in bilateral temporal foci, since corresponding areas on the left and right sides of the brain are connected with nerve fibers. (Consumer Summary produced by Reliance Medical Information, Inc.)

Secondary epileptogenesis is a well-established phenomenon in laboratory research. Focal epileptic seizures may be caused in a specific area of a test animal's brain by the chronic application of some stimulus, often a toxic substance, to that part of the brain. Signs of epileptic activity begin in the affected area, but then also emerge in the corresponding area on the other side of the brain. If the noxious stimulus is removed early, the seizure area on the opposite side of the brain disappears. If too much time elapses before the noxious stimulus is removed, the secondary epileptic focus on the opposite side of the brain has established itself and does not disappear. This secondary epileptogenesis, in which epileptic foci arise not from the primary cause but from the effects of other epileptic foci, has been difficult to ascertain in human patients, since toxic substances causing epilepsy can not be applied to and removed from human brains. However, in the December, 1991 issue of Archives of Neurology, researchers present findings which suggest that secondary epileptogenesis may occur in humans as well. The researchers studied patients whose epilepsy resulted from conditions such as fever and infection, which affect both sides of the brain, and conditions such as the growth of a tumor, in which only a specific area is affected. The researchers anticipated that epileptic seizure foci would occur in both temporal lobes more commonly among the patients who suffered fever or infection than among the patients with a brain lesion limited to one side. In fact, just the opposite was observed. Epileptic electrical activity was observed on both sides of the brain more commonly among the patients with one-sided brain lesions. Since the sequence of events can not be observed in a retrospective study of case records, it is impossible to say with certainty that the epileptic activity on the opposite side of the brain in these patients resulted secondarily from the primary epileptic focus near the primary cause. Nevertheless, these findings are very suggestive of secondary epileptogenesis as a cause of epileptic foci in humans as well as in animal models of epilepsy. (Consumer Summary produced by Reliance Medical Information, Inc.)

The brainwave tracings on an electroencephalogram are so complicated that it is almost impossible to tease out the information of direct concern from the background of electrical activity. One method of improving the recovery of useful information is to examine the evoked potential. Some sensory stimulus is applied, and in the moments that follow a series of brain events are electrically recorded that relate directly to the stimulus. One such event is the so-called P300. The P300 is defined as a positive wave which occurs at least 250 milliseconds (0.25 seconds) after the stimulus, and usually between 300 and 600 milliseconds after. At this time delay, the P300 does not represent the response of the brain to the stimulus itself; that process occurs much more rapidly. Rather the P300 relates in some fashion to the brain 'making sense' of the stimulus it has received. What, exactly, contributes to the P300 remains a matter for discussion, however. Even without understanding its precise source, P300 is nevertheless a useful tool for examining brain function in patients with various neurological impairments. P300 function was examined in 20 epileptic patients who were scheduled to undergo temporal lobectomy (removal of part of the temporal lobe). Ten patients were scheduled for left temporal lobectomy and 10 for right. Five healthy control subjects were also evaluated; all the control subjects were strongly right-handed. A printed word was presented to either the left or right visual field; in healthy subjects with a dominant left hemisphere, the response to a verbal stimulus is strongly dependent upon left or right presentation. However, in the epileptic patients there was no significant pattern of lateralized scalp P300 activity. Patients with left temporal lobe epilepsy showed reduced P300 activity compared with patients with right temporal disease, but it is thought that if the appropriate non-verbal stimulus were chosen, the right-hemisphere patients would have the reduced P300 response. In some patients, a P300 response could not be detected at all. Previous studies have examined the P300 response of epileptic subjects using depth electrodes; the present study not only confirms the abnormalities of the epileptic patients, but also demonstrates that it is possible to obtain useful recordings from the surface, as well. (Consumer Summary produced by Reliance Medical Information, Inc.)

Men with epilepsy can develop reproductive and sexual dysfunctions that may result from alterations in the hormonal output of the pituitary gland (the 'master' endocrine gland). Since the pituitary is under the control of the hypothalamus (a region in the brain), which sends releasing and inhibiting hormones to the pituitary, it is possible that seizures affect this delicate relationship. Gonadotropins (which stimulate the testes in the male and the ovary in the female) are one class of hormones secreted by the pituitary; this group includes luteinizing hormone (LH). To determine whether epilepsy is associated with abnormalities of LH secretion, 13 men with seizures in the temporal lobes of the brain and eight age-matched, non-epileptic control subjects were studied. Both groups were monitored for eight hours with EEG telemetry (constant measurement of the brain's electrical activity), and blood was drawn every 15 minutes for measurement of LH levels. Results showed no differences between patients and controls for the average baseline level and total level of LH secretion; in addition, the LH pulse amplitude (amount of a rapid increase) and frequency of pulses were the same. The epileptic patients, however, had more variability in their average baseline secretion and their pulse frequency, and nine patients had baseline LH levels that were either higher or lower than the normal range. Other LH pulse abnormalities were noted that correlated with the localization of the epileptiform (epileptic) electrical discharge pattern. It is possible that anticonvulsant medication led to the changes noted; however, no pattern was observed that seemed to correlate with the medication types or schedules. A hypothesis is presented regarding the ways that epilepsy and sexual and reproductive dysfunction could be related. The results support the possibility that epileptic activity affects the relationship between the pituitary and hypothalamus. (Consumer Summary produced by Reliance Medical Information, Inc.)

A wide variety of different underlying pathological processes may contribute to the seizures of epilepsy. In the extremely severe cases in which surgery is the last recourse, the portions of the brain removed sometimes are found to contain tumors while other no abnormalities are observed. Sometimes, even patients whose seizures are well controlled by drug therapy are ultimately found to have tumors many years after the initial onset of epilepsy. Positron emission tomography, or PET scanning, has proved to be useful in evaluating patients with uncontrolled complex partial seizures who are candidates for surgical treatment; the technique can reveal areas of depressed cellular metabolism within the brain. Nevertheless, the underlying pathological mechanisms that are responsible for the depressed metabolism often remain unknown. A study was undertaken of 26 patients undergoing surgery for intractable epilepsy to attempt to correlate the appearance of the brain prior to surgery with the pathological findings in the surgical specimens afterwards. Prior to surgery, the patients were evaluated with electroencephalography (EEG); computed tomography (CT) and magnetic resonance imaging (MRI), which are imaging techniques; and PET scanning, which can provide information about the brain's metabolism. Twenty-one of the 26 patients had depressed metabolism in the region corresponding to the seizure focus. Five patients had abnormalities of the seizure focus visible on MRI, while two others had MRI abnormalities that were located elsewhere in the brain, not at the place the seizures began. Eleven patients were found to have gliosis, a 'scarring' process indicating the brain is responding to some sort of damage. In ten of these patients, abnormalities had been detected on the PET scan. Three patients were found to have tumors; in two tumor patients, abnormalities were visible on CT. One tumor patient had a normal PET scan. The results of this study show that PET is a sensitive indicator of physiological abnormalities even when pathological analysis does not reveal any noticeable structural abnormalities. The study was not able to obtain sufficient information, however, to determine if any of the factors measured may be of value in predicting which patients are likely to benefit most from the surgical procedure. (Consumer Summary produced by Reliance Medical Information, Inc.)

Although many different factors can cause epilepsy, epilepsy with a secondary focus is thought to always have one origin, which is the epileptic discharges in another part of the brain. A special case of secondary discharges is the mirror focus, in which the primary and secondary discharges arise in the same place in the two opposite brain hemispheres. A secondary focus may become independent; that is, its discharge may no longer be time-related to discharges in the primary focus. To determine the incidence of independent secondary foci, and to identify any distinguishing characteristics, the electroencephalograms of 309 epileptic patients were examined. Of the total group, 41 patients had definite single one-sided foci and served as a comparison group. A total of 33, or 10.7 percent, had independent secondary foci. In 25 of these, the focus was of the 'mirror' variety. The records indicated that in 12 patients, the secondary focus started activity roughly at the same time as the primary focus. Most prevailing notions about the cause of the secondary focus attribute it to changes induced over time by epileptic activity in the primary focus. However, the observations in this study suggest that this explanation is not adequate to account for the existence of independent secondary epileptic foci. (Consumer Summary produced by Reliance Medical Information, Inc.)

In susceptible patients, flickering lights or repetitive patterns may stimulate the onset of a generalized epileptic seizure. Epileptic photosensitivity may occur in both primary generalized epilepsy and secondary epilepsy, in which the epilepsy results as a symptom of some other underlying disease process. It is well established that apomorphine is effective in eliminating the photosensitivity in patients with primary generalized epilepsy. A study was undertaken to determine if apomorphine might be effective in the treatment of secondary seizures as well. Seven patients were studied; their secondary seizures resulted from a variety of underlying causes such as Kufs' disease, juvenile neuraxonal dystrophy, and Baltic PME. All these conditions are classed as progressive myoclonus epilepsies (PME). (Myoclonus is the repetitive contraction and relaxation of muscles.) The patients were evaluated to determine which frequencies of flashing light were most effective at eliciting an abnormal brain response as recorded on the electroencephalograph (EEG). These flash frequencies were then used again after the administration of apomorphine; the photosensitive response was completely prevented in six patients and partially in the seventh. These results suggest that the underlying mechanism of photosensitivity in secondary epilepsies is similar to that in the primary generalized epilepsies. Apomorphine is an agonist of dopamine receptors, meaning that it ''competes for'' some of the same cell receptors as dopamine, a brain messenger involved in the inhibition of nerve signals. It is suspected that in photosensitive epilepsy, there is inadequate inhibitory effect exerted by dopamine on the cells of the visual cortex. Most likely, apomorphine prevents the development of seizures after light stimulus by restoring some of the inhibition of the visual cortex which normally should be provided by dopamine. (Consumer Summary produced by Reliance Medical Information, Inc.)

Surgery may be the last hope for patients with severe epilepsy who do not respond to any sort of medical treatment. Since epileptic seizures often begin at a single spot, or focus, in the brain and then spread to dominate the electrical activity of the whole brain, it is possible to help some patients with severe epilepsy by removing the portion of the brain containing the focus. In many surgically treated cases, the epileptic focus is located in the temporal lobe of the cerebral cortex or in the hippocampus, an adjacent structure. Clearly, the success of the surgical treatment depends upon how accurately the location of the epileptic focus can be determined prior to the operation. This may be done using scalp electrodes and electroencephalography (EEG). Greater accuracy may be obtained, however, using surgically implanted electrodes. These electrodes are of several varieties, including depth electrodes, which are long electrodes which penetrate into the affected brain area, and subdural electrodes, which lie on the surface of the brain but are placed under the dura mater, the tough fibrous sheath covering the brain. In a series of 47 patients whose epilepsy was unresponsive to medical treatment, both subdural and depth electrodes were used to compare the electrophysiological findings obtained with each type of electrode. The epileptic focus was successfully identified in 33 patients. In 23 cases, the focus was found with the depth electrodes. In six cases, both the depth electrodes and the subdural electrodes provided the location of the focus, and in four patients the subdural electrodes served to localized the foci. The results suggest that depth electrodes are more sensitive than subdural electrodes. The best information may be obtained by combining the information obtained from both methods. Surgery is considered only in cases of the most extreme and debilitating cases of epilepsy. In such severe cases, it seems justifiable to use invasive methods such as depth electrode recording, in order to provide the patient with the best possible chances of successful surgery should it actually be performed. (Consumer Summary produced by Reliance Medical Information, Inc.)

Byline: Pooja. Harijan, Arif. Khan, Nahin. Hussain Children and adolescents treated with antiepileptic drugs are known to have problems with bone metabolism, bone mineral density loss, and 2-3 times the [...]