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Sphenoidal electrodes: their use and value in the electroencephalographic investigation of complex partial epilepsy.

The diagnostic value of sphenoidal electrode EEG recordings in patients with seizures characteristic for epilepsy with complex partial symptomatology was assessed in a study comprising 404 patients; 71.3% of the patients had seizures with automatisms and amnesia, and 28.7% had psychic seizures with subjective phenomena such as hallucinations and illusions. A total of 59.6% of the patients had diagnostic EEG changes in routine waking or sleep EEG. In sphenoidal EEG recording including thiopenthone activation, diagnostic changes were found in 40.5% of the patients without specific changes in waking or sleep EEG, the chance of a positive finding being more than five times higher in patients with automatisms than patients with psychic seizures. Apart from cases where surgical treatment of temporal lobe epilepsy is considered, sphenoidal electrode EEG recording, including intravenous thiopenthone activation, should be performed in patients with seizure phenomena raising suspicion of epilepsy with complex partial symptomatology but where waking and sleep EEGs fail to demonstrate specific abnormalities.

Electrodes

Barbiturate effects on EEG abnormality in complex partial epilepsy.

Sixteen patients with drug-resistant complex partial epilepsy were, during preoperative investigations for surgical treatment, subjected to intravenous methohexital and amobarbital EEG activation tests. The interictal epileptic spike discharges were visually counted on the seizure-generating side and compared with those found in the contralateral hemisphere. The invasive recordings were made with depth electrodes implanted in the mesial temporal lobes of 5 patients, and with subdural strip electrodes in varying lateral positions over the frontotemporal-parietal lobes of the other 11 patients. The doses of 10% amobarbital, 50-200 mg, were too low to induce any significant activation. In eight patients with unilateral epileptic lesions, 10, 25 and 50 mg 1% methohexital, induced a dose-dependent increase in the interictal spiking, always higher on the side of the seizure-gererating focus. Asymmetric induction of beta activity was noted in five patients. The test gave valuable information when determining the type or location of the epileptic abnormality. Parallels were drawn with earlier studies on spike-activation tests after intracarotid amobarbital injections. Although administered differently, the barbiturates are supposed to act directly on the neurons, and not via integrative wakening mechanisms.

Adult

Spike voltage topography and equivalent dipole localization in complex partial epilepsy.

The EEG of 45 patients with complex partial epilepsy was recorded from standard and supplementary inferior temporal electrode sites for 2 or more days via cable telemetry onto video (VHS) tape (22-25 channels, common reference). Epochs with "temporal spikes" were read into a topographic EEG device where individual spikes were visually identified and averaged in sums of 8-32. Analysis of spike voltage topography revealed two distinct patterns - dipolar, Type 1 and non-dipolar, Type 2. One or the other spike type predominated in all but two patients. Application of source modeling techniques (3 shells, single dipole, 6 parameters) to the spike topography data revealed that both spike types had similar equivalent dipoles in terms of location and orientation, except for vector elevation. However, calculated dipoles for Type 1 spikes were more stable over the course of the spike peak. Correlations with clinical data and intracranial EEG suggest that Type 1 spikes originate in mesial temporal structures, while Type 2 spikes arise from temporal or frontal neocortex. Spike voltage topography and equivalent dipole localization appear to be useful in the presurgical evaluation of patients with focal epilepsy.

Action Potentials

Effect of commissurotomy on complex partial epilepsy in patients without a resectable seizure focus.

Twenty-five patients in a series of 51 undergoing partial or complete section of the corpus callosum for the treatment of intractable epilepsy experienced complex partial seizures among their seizure types preoperatively. Ten of these 25 patients have experienced no further complex partial seizures. Reduction in severity of seizures has been found in 11 of the 15 patients still experiencing this seizure type, and 3 have had greater than 80% frequency reduction. These findings are consistent with the electrophysiologic observations of Lieb on the relative unimportance of the hippocampal commissure in man and the behavioral observations of Quesney on unilateral versus bilateral temporal lobe seizure activity.

Corpus Callosum

Memory effects following carbamazepine monotherapy in patients with complex partial epilepsy.

To evaluate the memory effects of carbamazepine (CBZ) monotherapy, a relatively large computerized neuropsychological test battery, specially developed to assess the properties of different memory systems, was administered to a group of patients with epilepsy in a pre-test--post-test control group design. Consistent with previous findings, the results show that CBZ treatment does not induce any general important or consistent negative signs of memory dysfunction. However, the epilepsy group as such demonstrates a relative inability to carry out more complex working memory tasks and they are also slower in simple long-term memory access tasks. Finally, the detailed findings suggest that CBZ plasma concentration levels within the therapeutic range are highly and negatively associated with short-term recency, which is a novel finding.

Adult

Visual half-field testing of memory functions in patients considered for surgical treatment of intractable complex partial epilepsy.

The present research employed the visual half-field (VHF) technique to assess memory functions in normal subjects and in patients with unilateral temporal lobe epilepsy prior to surgery. Two studies were conducted. In Study 1, concrete and abstract words were presented to the left (LVF) or the right visual half field (RVF), and measures were made of response latencies, naming, free recall, and recognition. In Study 2, pictures depicting random shapes with low verbal association values were presented, and measures were made of latencies for identification and recognition of the shapes. Overall, the results showed a RVF advantage for words, but no lateralization for shapes. A selective hemisphere memory deficit was obtained for abstract words in patients with left temporal lobe lesions. Otherwise, no obvious lesion-related differences were found in the preoperative analyses. It is concluded that VHF testing of verbal information, but not abstract visuo-spatial information, is discriminative in assessing hemispheric functions in normal subjects and patients with temporal-lobe epileptic lesions.

Adult

Genetics of the partial epilepsies: a review.

The research literature is consistent in reporting somewhat less familial aggregation in partial than in generalized epilepsy. However, relatives of patients with partial seizures do appear to have higher seizure risks than relatives of controls, suggesting that genetic factors are important in at least some partial epilepsies. Complex partial epilepsy appears to be only slightly less familial than other types of epilepsy. Relatives of patients with focal EEG abnormalities generally have been found to have lower risk of both EEG abnormalities and epilepsy than relatives of patients with generalized abnormalities. For focal temporocentral abnormalities, however, there is evidence of an important influence of genetic factors.

Disease Susceptibility

EEG dipole modeling in complex partial epilepsy.

Visual inspection and qualitative impressions of clinical EEG abnormalities are being replaced by quantitative characterization of scalp voltage fields and dipole modeling of underlying cerebral sources. Three approaches have been used in the analysis of focal spikes of complex partial epilepsy. 1) Instantaneous, single dipole, inverse solutions for the voltage topography of the spike peak have revealed two distinct equivalent dipole configurations in the brain lobe beneath the negative extreme-radial and oblique (mixed radial and tangential). Only radial dipoles have been found for frontal and fronto-central spikes, while either type have been found for temporal and occipital spike foci. 2) Dipole stability can be assessed by an inspection of sequential instantaneous solutions encompassing the spike complex or by calculating the standard deviation of dipole location (x,y,z) and orientation (elevation, azimuth) parameters during this period. Two-thirds of spike dipoles of the radial type and essentially all of the oblique equivalent dipoles were found to be stable, whereas one-third of the radial dipoles were unstable in position or orientation. 3) Spatio-temporal analysis can identify multiple underlying sources and their potentials. Modeling separate radial and tangential dipoles over the course of the spike has revealed a composite character for spike fields with oblique dipoles and often has defined leads or lags in activity that suggested propagation between infero-mesial and lateral temporal cortex. Correlations with clinical and intracranial EEG data suggest that patients with mesial temporal sclerosis have spikes with oblique and stable equivalent dipoles; patients with discrete cortical lesions have spikes with radial and stable dipoles; patients with extensive or multi-focal cortical insults have spikes with radial and unstable dipoles.

Action Potentials

Benign complex partial epilepsies in infancy.

Nine infants with benign complex partial seizures, diagnosed by simultaneous electroencephalogram and video recordings, are described. At mostly 3-10 months of age, these infants demonstrated clusters of seizures which consisted of motion arrest, decreased responsiveness, staring or blank eyes mostly with simple automatisms, and mild convulsive movements associated with focal paroxysmal discharges. The seizures were controlled easily with carbamazepine or phenobarbital and all patients remained seizure-free for more than 3 years. Four patients had family histories of benign types of infantile convulsions. Interictal electroencephalogram and psychomotor development were normal in all patients.

Carbamazepine

Effects of single doses of vigabatrin on CSF concentrations of GABA, homocarnosine, homovanillic acid and 5-hydroxyindoleacetic acid in patients with complex partial epilepsy.

Vigabatrin, as a single oral dose of 50 mg/kg, was administered to 11 patients with drug-refractory complex partial epilepsy. Serial lumbar punctures were performed prior to and 5 times within the first week following treatment. Cerebrospinal fluid (CSF) concentrations of total GABA, free GABA, homocarnosine, homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA) and vigabatrin were determined as well as blood vigabatrin levels. CSF GABA, homocarnosine, HVA and 5-HIAA concentrations increased by 6 h after the single dose and remained elevated for up to 5-7 days. In contrast, CSF and blood vigabatrin levels were maximal within the first 24 h and were no longer detectable thereafter. Hence, these results are consistent with vigabatrin acting as an irreversible inhibitor of GABA-transaminase and suggest that it may also increase biogenic amine turnover.

Administration, Oral

The critical evaluation of the late results after temporal lobectomy performed because of medically refractory complex partial epilepsy (CPE).

Basing on a follow-up study till 27 years of a group of 50 young patients suffering on medically refractory complex partial epilepsy which were treated by temporal lobectomy the author has reached a complete seizure-free result in 66% of them. A critical evaluation of the transient disadaptation syndrome and of a permanent amnesic syndrome in a part of them as well as psychometric memory tests have been performed. The pathophysiological interpretation of the results and selection criteria for the efficient temporal lobectomy have been proposed.

Amnesia

Temporal intermittent rhythmic delta activity (TIRDA) in the diagnosis of complex partial epilepsy: sensitivity, specificity and predictive value.

Temporal interictal rhythmic delta activity or TIRDA was found in 45 of the 127 recordings of patients with complex partial epilepsy (CPE) referred for both awake and sleep EEG. TIRDA was more abundant during drowsiness and light sleep; it occurred more characteristically as trains of 50-100 microv sinusoidal or saw-toothed 1-4Hz activity, recorded predominantly from anterior temporal regions. When occurring bilaterally and independently, TIRDA varied from side to side. TIRDA is often found in association with anterior temporal spikes or sharp waves (TS) particularly during sleep, as observed in 43 out of 45 EEGs. TIRDA can nevertheless occur as an isolated abnormality, as noted in two sleep and 12 awake study recordings. Because of its high specificity and positive predictive value over a large range of prevalence, TIRDA should be singled out as an accurate interictal indicator of CPE. In patients with isolated TIRDA, the cost of prolonged EEG recording during sleep for the purpose of activating TS has to be weighed against the yield of eventually confirming the obvious.

Adult

Excitotoxic amino acid receptors in human complex partial epilepsy.

It has long been recognized that mesial temporal sclerosis is the most common pathologic finding in temporal lobes removed for the treatment of medically refractory complex partial epilepsy. The regions of the hippocampus most vulnerable contain the highest densities of excitatory amino acid receptors in the brain. We used receptor autoradiography to determine the density of N-methyl-D-aspartate (NMDA) and kainic acid (KA) receptors from 5 patients undergoing such surgery and compared the findings with 6 specimens obtained at postmortem. A 2-fold increase in the density of NMDA receptors and an increased density of KA receptors was found in entorhinal cortex in epileptic specimens. Loss of NMDA and KA receptor density was apparent in the sclerotic regions CA3 and CA1, but not in other areas of the hippocampus or dentate gyrus. These findings suggest that damage in the hippocampus may result, at least in part, from the presence of aberrant excitatory circuits in the entorhinal cortex.

Autoradiography

Double-blind dose reduction study of vigabatrin in complex partial epilepsy.

Seventy-five epilepsy patients with at least two complex partial seizures/month were treated with gamma-vinyl GABA (GVG) 3 g/day for 3 months. Forty-one patients (54%) showed a reduction of greater than or equal to 50% in seizures. The median monthly seizure frequency decreased from 11.5 to 4 seizures/month. Twenty percent of patients had an improvement in general performance without a significant reduction in seizures. The responders entered the second phase of the study, in which 28 patients were randomly allocated to 3 g/day and 25 patients to 1.5 g/day GVG under double-blind conditions. The dosage of 3 g/day appeared to be clearly more effective than 1.5 g/day. However, even with 1.5 g/day GVG the seizure frequency was significantly reduced as compared to baseline. Drowsiness was the most commonly observed side effect, and it diminished with continued treatment. In three cases side effects led to the withdrawal of GVG therapy.

Adolescent

Somatostatin, beta-endorphin, and prolactin levels in human cerebrospinal fluid during the gamma-vinyl-GABA treatment of patients with complex partial epilepsy.

The anticonvulsant action of the new anticonvulsant drug gamma-vinyl-GABA (GVG) is obviously mediated by elevation of the concentration of GABA in the brain. The effect of GVG administration on other transmitter systems is not fully known in humans. We studied the possible interactions of GVG administration with peptidergic systems. Included in this study were 67 patients with complex partial epilepsy (CPS). The first CSF sample was taken before GVG administration. The second CSF sample was taken after 3 months of GVG treatment (3 g/day). Thereafter half of the responders (50% decrease in seizure frequency or clear improvement in global performance) received 3 g/day and the other half received 1.5 g/day for the next three months, after which the third CSF sample was taken. Somatostatin (SLI), beta-endorphin (beta-EP), and prolactin (PROL) levels in CSF were measured by radioimmunoassay. Total GABA (tGABA) and GVG levels in CSF were measured by high performance liquid chromatography. After 3 months of GVG treatment there was a slight increase in the beta-EP (p = 0.027, Student's paired t-test), which was not found after 6 months of GVG administration. Both SLI and PROL were stable during the study. Peptide levels were not connected to the clinical response to GVG, GVG dosage, or to tGABA levels in the CSF. In conclusion, the elevation of GABA levels in the brain during GVG treatment apparently does not induce long-term interactions with the peptidergic systems studied.

Adult

Effect of gamma-vinyl GABA treatment on cholinergic and aminergic neurotransmission and on cyclic nucleotides in human complex partial epilepsy--a CSF study.

1. Gamma-vinyl GABA (GVG) is a new anticonvulsant drug that enhances levels of GABA in the brain by irreversibly inhibiting GABA transaminase. 2. To further evaluate the effects and mechanism of action of GVG in the human brain, we measured acetylcholinesterase (AChE) activity and levels of homovanillic acid (HVA), 5-hydroxyindoleacetic acid (5-HIAA), cyclic nucleotides (cAMP, cGMP), total GABA (TGABA), and GVG in CSF of 78 patients with complex partial epilepsy. The CSF samples were taken at baseline and after 3 months of GVG administration (3 g GVG per day). Thereafter, the responders (= 50% decrease in number of seizures) were divided (double-blind) into two groups that received either 1.5 g or 3 g of GVG per day for the next 3 months. The third CSF sample was taken after this double-blind period. 3. TGABA levels were increased during the GVG treatment (p less than 0.001). In the whole group of patients AChE, HVA, 5-HIAA, and cAMP did not differ from baseline values, cGMP levels were slightly elevated after 3 months of GVG administration (p = 0.019), but were no longer elevated after 6 months. Responders had slightly lower AChE activity than nonresponders (p = 0.041). After 6 months of drug treatment the cGMP levels of patients receiving 1.5 g of GVG did not differ from those receiving 3 g. 4. In conclusion, GVG administration elevates levels of TGABA in the CSF without any clear of constant change to cholinergic and aminergic transmission or effect on cyclic nucleotides. Our study further emphasizes the specific mechanism of action of GVG via GABAergic transmission.

Acetylcholinesterase

Fentanyl-induced electrocorticographic seizures in patients with complex partial epilepsy.

Although electrical seizure activity in response to opioids such as fentanyl has been well described in animals, scalp electroencephalographic (EEG) recordings have failed to demonstrate epileptiform activity following narcotic administration in humans. The purpose of this study was to determine whether fentanyl is capable of evoking electrical seizure activity in patients with complex partial (temporal lobe) seizures. Nine patients were studied in whom recording electrode arrays had been placed in the bitemporal epidural space several days earlier to determine which temporal lobe gave rise to their seizures. The symptomatic temporal lobe was localized by correlating clinical and electrical seizure activity obtained during continuous simultaneous videotape and epidural EEG monitoring. In each patient, clinical seizures and electrical seizure activity were consistently demonstrated to arise unilaterally from one temporal lobe (four on the right, five on the left). During fentanyl induction of anesthesia in preparation for secondary craniotomy for anterior temporal lobectomy, eight of the nine patients exhibited electrical seizure activity at fentanyl doses ranging from 17.7 to 35.71 micrograms.kg-1 (mean 25.75 micrograms.kg-1). More importantly, four of these eight seizures occurred initially in the "healthy" temporal lobe contralateral to the surgically resected lobe from which the clinical seizures had been shown to arise. These findings indicate that, in patients with complex partial seizures, moderate doses of fentanyl can evoke electrical seizure activity. The results of this study could have important implications for neurosurgical centers where electrocorticography is used during surgery for the purpose of determining the extent of the resection.

Adult