Vagal nerve stimulation does not unkindle seizures.

The purpose of this study was to investigate a mechanism of action for the effect of vagal nerve stimulation on reducing seizures in patients with complex partial epilepsy. The hypothesis tested was that vagal nerve stimulation has an antikindling effect on epilepsy. The databases of two large clinical trials (E03, E05) were accessed, and statistical methods were applied using logarithmic transforms and regression analysis. Two parameters--duration of a patient's epilepsy before entering the clinical trial and the patient's seizure density before entering the clinical trial--were used as markers of subsequent seizure control during vagal nerve stimulation. In general, there was not a good fit to the regression lines, and the slope of the lines did not conform to the hypothesis. The hypothesis that vagal nerve stimulation may unkindle epileptic seizures was not supported.

Specialty care for patients with epilepsy must become standard of care. Promotion of Specialty Care for Epilepsy Group.

Epilepsy is a complex, common disorder with severe consequences for patients. The authors believe that a significant percentage of patients are receiving suboptimal care. The national standard of care needs to be upgraded to include the notion that patients with less than total seizure control or those suffering from any medication side-effects should be given the opportunity to receive specialty care by physicians with specific expertise in the field of epilepsy.

Anesthetic implications of epilepsy, status epilepticus, and epilepsy surgery.

Epilepsy is a clinical paroxysmal disorder of recurring seizures, excluding alcohol or drug withdrawal seizures or such recurring exogenous events as repeated insulin-induced hypoglycemia. Epilepsy has a profound impact on each individual diagnosed with this disease. Seizures have been and are thought to arise as a result of abnormalities in (a) neural circuits, (b) excitation/inhibition balance, (c) potassium, and (d) genetic abnormalities. Therapy for epilepsy is either medical, entailing the use of a variety of antiepileptic drugs, or surgical. An urgent approach to seizure control is indicated when status epilepticus occurs. When all standard therapy fails, general anesthesia can be used to control status epilepticus. Surgery is an option in the treatment of epilepsy and requires extensive preoperative evaluation. The primary concerns for the neuroanesthesiologist anesthetizing the patient with epilepsy are the capacity of anesthetics to modulate or potentiate seizure activity and the interaction of anesthetic drugs with antiepileptic drugs. Proconvulsant and anticonvulsant properties have been reported for nearly every anesthetic. If seizure spikes are to be evoked during seizure surgery, then light anesthesia with a proconvulsant anesthetic is used. Conscious analgesia can be used for awake seizure surgery. However, if electrocorticography is not planned, then a general anticonvulsant anesthetic maintenance regimen is used. The latter technique also may be useful in patients whose anesthetic management is complicated by an incidental history of epilepsy.

Polarization anatomy of a kainic acid seizure.

Slow voltage-sensitive dyes work by accumulating in brain tissue and report the average membrane potential of neurons and glia. The voltage-sensitive dye diO-C2-5 was used to monitor the polarization state of 27 brain structures in the rat during a systemically induced, behaviorally mild, kainic acid seizure using a 20 s recording period. The effects of the anesthetic agent used in the experiment were minimized by delaying the dye injection and seizure mapping for one day. Eleven areas were depolarized during the seizure, but 16 other areas did not change their polarization state compared to controls. The effects of pentobarbital appear to have no measurable effect on seizure propagation once the animal has behaviorally recovered from the anesthesia. The technique allows for mapping areas of seizure involvement with a unique combination of spatial and temporal resolution.

Linear intracerebral calcification after depth electrode implantation.

We report linear calcifications along the trajectories of previously implanted depth electrodes in 2 patients. A 20-year-old man and a 38-year-old woman with medically intractable complex partial seizures (CPS), underwent bilateral frontal and mesiotemporal depth electrode implantation as part of their epilepsy surgery workup. Brain computed tomography (CT) at that time was normal (except for cerebrellar atrophy in one case). One patient had a left anterotemporal lobectomy (ATL), and the other declined operation. Subsequent CT scans showed linear calcifications 1-2 cm long in the occipital lobes (unilateral in 1 and bilateral in the other) that followed the trajectories of the temporal depth electrodes. This finding remained unchanged at latest follow-up (2-2.5 years), and no new pathology has appeared on subsequent scans. No abnormalities of calcium metabolism were detected. Review of all available CT scans of our patients with a history of previous depth electrode implantation showed no additional similar cases. We believe this is the first report of intracerebral calcifications after depth electrode implantation.

Epilepsy brain surgery: a Pittsburgh perspective.

The views of the authors are presented about the past history and recent situation of epilepsy brain surgery in the United States. Issues of efficacy and quality of life are reviewed, and little empirical evidence is found supporting epilepsy brain surgery as a cost-effective treatment modality. Prospective randomized clinical trials have not been run to address these issues and various problems with patient recruitment and funding seem destined to preclude them.

Evaluation of the thiopental test in epilepsy surgery patients.

One hundred and three patients underwent a thiopental test during a presurgical evaluation for epilepsy surgery. Depth electrodes were implanted bilaterally into the mesial temporal and mesial frontal lobes. Thiopental was infused at 25 mg/30 s for adults and 0.3 mg/kg/20 s in children until loss of corneal reflexes or a total of 1 g. The absence of beta activity on the EEG, and activation of interictal spiking were two parameters monitored at all recording sites. Positive results were correlated with the anatomy of the ictal epileptic foci. Half of the patients produced increased interictal spiking and three-quarters of them showed absence of beta production in at least one lobe. Despite a reasonably high concordance between ictal foci and the two thiopental parameters, both measures yielded a low sensitivity and specificity. This work, as well as that reported in the literature, was unable to confirm the hypothesis that local damage within the temporal lobe was responsible for positive thiopental test results. An alternative hypothesis is proposed that the thalamus may be a distant source of these findings. Irrespective of the mechanism, the thiopental test must be used cautiously in the evaluation for epilepsy surgery.

Anesthetic care during thiopental tests to evaluate epileptic patients for surgical therapy.

A thiopental test 2 weeks after insertion of intracranial electrodes may be used to evaluate patients with refractory epilepsy for surgical therapy. Barbiturates normally produce beta activity on the electroencephalogram. The absence of this response in a monitored brain region implies focal cerebral dysfunction. We describe a technique used to perform this test and the resultant morbidity. The thiopental test consists of intravenous injection of thiopental, 25 mg, every 30 s until either corneal reflexes are abolished, 1,000 mg of thiopental has been administered, or adverse events occur. In children, the dose is adjusted to approximately 0.3 mg/kg of thiopental every 20 s. A retrospective chart review was performed on 104 patients who underwent thiopental tests at the University of Pittsburgh Epilepsy Center. Records were systematically reviewed for thiopental dose, mean arterial blood pressure, heart rate, oxygen saturation in arterial blood, time to responsivity, need for airway intervention, and occurrence of nausea or vomiting. Thirty-six patients developed upper airway obstruction which required jaw lift maneuver, six patients were given 1,000 mg of thiopental without loss of corneal reflexes, and one patient briefly sustained an arterial saturation of 67%. Five patients exhibited electrographic seizures with clinical seizures evident in two patients. No permanent effects were evident in any patient as a consequence of the test. We conclude, with appropriate monitoring and personnel, that the thiopental test, as described, can be performed safely with acceptable morbidity.

Memory performance during the Amytal test in patients with non-temporal lobe epilepsy.

PROBLEM: The amobarbital (Amytal) sodium test has been considered an indispensable tool in the presurgical examination of patients for epilepsy surgery. However, the accuracy of the Amytal test for predicting memory deficits, especially the amnestic syndrome, has been questioned. METHOD: The Amytal test was administered bilaterally to three groups of patients with epilepsy: temporal lobe (n = 76), frontal lobe (n = 25), and primary generalized (n = 8). Each injected hemisphere for each patient was graded pass or fail for its ability to support memory. RESULTS: The percentages of hemispheres that failed the Amytal test were 31% for the temporal lobe group, 32% for the frontal lobe group, and 56% for the primary generalized group. CONCLUSIONS: The Amytal test may be a sensitive measure of memory dysfunction. However, the high percentage of failures remains at variance with the rare incidence of the amnestic syndrome, suggesting a low specificity for this test.

Characterization of intractable juvenile myoclonic epilepsy: new perspectives on primarily generalized seizures.

Twelve patients were identified at an epilepsy center who had medically intractable juvenile myoclonic epilepsy. Significant characterization of this group included the long duration of their epilepsy (averaging 21 years) during which the diagnosis and appropriate treatment was delayed. A high percentage of these patients had asymmetries or focal discharges on scalp EEG (6 of 9 patients). A review of the literature and the findings in these 12 patients lead to the conclusion that juvenile myoclonic epilepsy is not necessarily a benign epilepsy. Alternative therapies, such as epilepsy surgery, may be indicated in such extreme cases.

In vivo mapping of drug-induced seizures with voltage-sensitive dye.

The voltage-sensitive dye diO-C2-5 was used to produce an in vivo map of the membrane potential in two types of seizures. Mild limbic seizures were induced in rats with kainic acid; clonic convulsive seizures were induced with bicuculline. Kainic acid animals showed various levels of neural depolarization during their seizures in limbic, thalamic, cortical, and brainstem sites. The bicuculline animals showed uniformly greater levels of neural depolarization during their seizures. The magnitude of these changes relative to controls varied across seizure models and reflected the different underlying neural mechanisms for each model. The ability of the technique to capture local electrical events provides a new tool in which to explore brain activity.

A review of interictal cerebral blood flow in the evaluation of patients for epilepsy surgery.

The literature on cerebral blood flow (CBF) studies in patients with epilepsy is critically reviewed. Two methods are specifically addressed, radioactive xenon delivered through inhalation or vascularly, and single photon emission computed tomography (SPECT) using various tracers. Both regional and global blood flow were used in these studies to assess focal and generalized seizures. Electroencephalogram (EEG) foci were determined by various techniques, including interictal and ictal recordings from scalp or intracranial electrodes. All studies reported a positive concordance between EEG foci and CBF. However, there was a high incidence of false positive and false negative results. The methodology of almost all of the studies was inadequate to assess accurately the sensitivity and specificity of CBF to localize the seizure focus. Even when conservative estimates were made, the sensitivity and specificity of CBF was too low to be used as a diagnostic test for epilepsy, and inadequate to localize the EEG focus in the evaluation of patients for epilepsy surgery.

Seizure circuit analysis with voltage sensitive dye.

Voltage sensitive dye was used to produce a map of average membrane polarization for the purpose of analysing the circuitry involved in seizures. Dorsal hippocampus, ventral hippocampus, entorhinal cortex, substantia nigra and occipital cortex were selected to calculate the relative changes in polarization. Rats were induced with bicuculline to have convulsive seizures and mild limbic seizures with kainic acid. A 20 second sample of these seizures were recorded using the voltage sensitive dye. Control animals showed a relatively uniform polarization state in the five brain areas. The bicuculline seizure produced hyperpolarization in all five areas. The magnitude of the hyperpolarization varied among the regions to produce a distinctive pattern. The kainic acid seizure produced depolarization in the four limbic areas. The magnitude of the depolarization also varied, producing a different pattern compared with bicuculline or control. Future applications of this technique in animal models could help identify those areas in the brain which regulate seizure propagation, and the anatomical loci in which antiepileptic drugs interfere with this propagation. Ultimately, human applications would include linking voltage sensitive dyes with paramagnetic or positron emitting traces so that epileptic processes could be visualized using magnetic resonance imaging or positron emission computed tomography.

Visual angle of the mind's eye before and after unilateral occipital lobectomy.

Do mental images occur in a spatially mapped (i.e., analog, or array-format) representational medium? Kosslyn's (1978) method was used to measure the visual angle of "the mind's eye" to estimate the extent of the imagery medium before and after unilateral occipital lobectomy. It was found that the overall size of the largest possible image was reduced following the surgery. In addition, only the horizontal extent, and not the vertical extent, of the imagery medium was reduced. Finally, it was determined that the S understood the tasks, was not aware of our predictions, and was unaffected by a strong demand characteristic in a different imagery task. These results are consistent with the hypothesis that imagery occurs in a spatially mapped representational medium dependent on occipital cortex.

Role of the frontal lobes in the propagation of mesial temporal lobe seizures.

The depth ictal electroencephalographic (EEG) propagation sequence accompanying 78 complex partial seizures of mesial temporal origin was reviewed in 24 patients (15 from the University of Pittsburgh Epilepsy Center and 9 from UCLA). All patients were monitored with bilateral mesial frontal and mesial temporal depth electrodes and later received anterior temporal lobectomy. Ictal EEG records were categorized according to sequence of spread from the temporal focus to the other regions. Although propagation patterns varied both within and between patients, certain features were notable: (a) It was very common for seizure activity to spread initially to the ipsilateral frontal lobe (observed in 22 of 24 patients). (b) The most common mode of spread (15 of 24 patients) was initiating temporal lobe----ipsilateral frontal lobe----contralateral frontal lobe----contralateral temporal lobe. (c) Occasionally, seizure discharges invaded the frontal lobes but failed to invade the contralateral temporal lobe (2 of 24 patients). (d) Seizure activity occasionally invaded the contralateral temporal lobe prior to invading the frontal lobes (2 of 24 patients). Other notable features included (i) a clear tendency for mesial temporal seizure discharges initially to invade orbitofrontal (as opposed to anterior cingulate) cortex and (ii) the emergence of a period of clear asymmetry in the frontal lobes during which high-amplitude, rapid discharges were present on the side ipsilateral to the initiating temporal lobe. These results suggest that the prefrontal region, especially the orbitofrontal cortex, is strongly influenced by mesial temporal ictal activity. This region appears to be frequently involved in the propagation of seizures initiated in the mesial temporal lobe and may play a role in the interhemispheric propagation of mesial temporal seizures.