Interdependence of different genetic EEG patterns in siblings of epileptic patients

The present study is based on the data of a more extensive investigation of the genetics of spike-wave epilepsies of childhood with minor seizures (Doose and Baier 1987). It evaluated EEG findings in 271 siblings of patients by means of log-linear methods. The risk of siblings to manifest spikes and waves during rest or hyperventilation is distinctly increased if they are positive for 4-7 Hz rhythms, and to a lesser degree, if they are photosensitive. Moreover, siblings of female patients seem to be at a higher risk of manifest spikes and waves than siblings of males. 4-7 Hz rhythms of the EEG background activity and photosensitivity are mutually independent symptoms of an increased liability to manifest spikes and waves. These findings are discussed in the context of a 'multifactorial' background of spikes and waves.     

EEG changes in patients during the introduction of carbamazepine.

This study evaluates the EEG changes during the standardized introduction of carbamazepine in 16 previously untreated neurological patients and their relationship to serum levels of carbamazepine and carbamazepine-10,11-epoxide. Therapy was started with a dosage of 400 mg carbamazepine b.i.d. and remained unchanged during the whole study period of 35 days. Frequency analysis of serial EEG records was performed by Fast Fourier Transformation. In comparison to the pretreatment period (1) the mean values of the total power and relative powers of the theta and delta bands increased and (2) the mean values of the relative power of the alpha band and the center frequency decreased. These changes were already established 3 days after the beginning of the treatment and remained constant during the observation period. There were marked interindividual differences. (3) There was no statistically significant correlation between serum levels of carbamazepine or carbamazepine-10,11-epoxide and the EEG parameters. Our results demonstrate that the degree of EEG change primarily reflects individual susceptibility to carbamazepine and its metabolite during the early stage of carbamazepine exposure and is not dose related.     

EEG changes after withdrawal of medication in epileptic patients.

Fifty-five patients with intractable partial seizures whose on-medication EEGs demonstrated either predominantly focal epileptiform lesions or absence of paroxysmal activity, were studied, and the effect of withdrawing all anticonvulsive drugs on their EEGs was observed. Four types of response were encountered: (1) no effect (20%); (2) specific (focal) activation (25%); (3) complex activation (29%) with widespread of the initial on-medication focus or appearance of the additional independent epileptogenic foci; and (4) "non-specific" activation (63%), consisting of bursts of either bilaterally synchronous and frontally dominant spike and waves, triphasic waves, or sharp slow complexes, or smaller amplitude rapid and diffuse spike-and-wave complexes. This latter effect is thought to be secondary to metabolic derangements resulting from the withdrawal of neurotropic agents and not directly related to the specific epileptogenic process. No association was found between type of effect and any of the following parameters: topography of on-medication focus, duration of therapy, type of anticonvulsant used, suspected underlying etiopathology, or median age when medication was withdrawnn. Furthermore no evidence could be found that the development of a "complex" or "non-specific" EEG effect carried with it a bad prognosis for surgical cure following focal cortical excision. Performing off-medication tracings seems to be of greatest value in patients with partial seizures and EEGs revealing either a relative paucity of definite absence of epileptiform discharges. The occurrence of a "non-specific" response in a questionable epileptic during the off-medication period, on the other hand, should be interpreted with caution.     

Effects of phenytoin and carbamazepine on cognitive functions in newly diagnosed epileptic patients

Phenytoin (PT) and carbamazepine (CBZ) are the two most prescribed anticonvulsants in Finland. Their effect on the cognitive functions of 43 newly diagnosed epileptic patients was examined. The medication was randomly assigned. The patients were tested before the medication was started, and after half a year's therapy. In order to estimate the practice effect in repeated testing a control group of 21 volunteers was similarly tested and retested. Both anticonvulsants, PT in particular, decrease the normal practice effect observed in neuropsychological testing. Compared to the CBZ group, patients with PT became somewhat slower, and their visual memory decreased. Within the PT group the motor slowing was more marked in female patients, and in patients having higher PT serum levels. In PT and CBZ groups there was an equal decrease in negative mood i.e. tension, depression, bewilderment and irritability.     

Utilization patterns of community mental health services by newly referred patients

Summary The present study compared the pattern of service utilization over a 1-year period, of 349 newly referred adult patients to the four community mental health clinics in Jerusalem. Treatment in these clinics is provided free of charge and there are no limits on length of treatment. Irrespective of patient diagnosis and clinic setting, the percentage of patients remaining in contact with the clinics declined sharply during the first 3 months, and after 6 months stabilized to around 25–40%. However, among patients with nonmajor psychiatric disorders, inter-clinic variation in compliance with treatment was observed. In clinics with a long-term psychotherapeutic orientation, a larger proportion of patients was referred to other services following intake, and a larger proportion of patients dropped out of treatment. In these clinics, more patients were placed on waiting lists before beginning treatment, and the drop-out rate among these patients was significantly higher than that of patients in treatment. The implications of these results for treatment policy in public services are discussed.     

甲氧明对青霉素致癎大鼠发作行为与皮层脑电图的影响

目的探讨α1受体激动剂甲氧明对青霉素致癎大鼠发作行为学与皮层脑电图的影响。方法建立大鼠青霉素点燃模型,分别腹腔注射或海马注射甲氧明,按照改良racine分级标准,观察对大鼠发作行为学的影响以及皮层脑电图的变化。结果甲氧明腹腔注射预处理组达到I级的潜伏期(32.5±12.4)min比生理盐水组(15.2±8.1)min明显延长;甲氧明组racine分级均在Ⅱ级或Ⅱ级以下,生理盐水组全部达到Ⅳ级(P<0.01)。海马注射甲氧明预处理组脑电图癎性放电潜伏期(24′6″±5′53’″)较空白组(8′41″±1′13″)和生理盐水组(6′31″±1′43″)明显延长;生理盐水组与未预先处理组无明显统计学差异。与腹腔注射生理盐水相比,腹腔注射甲氧明对脑电图癎性放电改变没有统计学差异(P>0.05),海马注射甲氧明组与海马注射生理盐水组有明显统计学差异(P<0.01),海马注射甲氧明可以减少性放电。结论甲氧明延缓青霉素诱导癫癎的发展进程并降低癎性发作强度;甲氧明海马注射抑制青霉素癫癎模型皮层脑电图性放电程度;中枢α1肾上腺素受体参与青霉素诱导癫癎的抑制作用。     

Effect of viloxazine on serum carbamazepine levels in epileptic patients

The present study describes the interaction between carbamazepine (CBZ) and viloxazine, a recently synthesized antidepressant agent. Seven epileptic patients on chronic anticonvulsant therapy showed a significant (p less than 0.005) increase in steady-state serum CBZ levels (from 8.1 +/- 2.5 SD to 12.1 +/- 2.5 SD micrograms/ml) when viloxazine (300 mg/day) was added to the therapy. The effect was associated with the appearance of mild CBZ intoxication. The symptoms of this intoxication (i.e., dizziness, ataxia, fatigue, drowsiness) disappeared rapidly, and serum CBZ levels decreased to the basal values, when viloxazine administration was stopped.     

EEG changes in patients during the introduction of carbamazepine

This study evaluates the EEG changes during the standardized introduction of carbamazepine in 16 previously untreated neurological patients and their relationship to serum levels of carbamazepine and carbamazepine-10,11-epoxide. Therapy was started with a dosage of 400 mg carbamazepine b.i.d. and remained unchanged during the whole study period of 35 days. Frequency analysis of serial EEG records was performed by Fast Fourier Transformation. In comparison to the pretreatment period (1) the mean values of the total power and relative powers of the theta and delta bands increased and (2) the mean values of the relative power of the alpha band and the center frequency decreased. These changes were already established 3 days after the beginning of the treatment and remained constant during the observation period. There were marked interindividual differences. (3) There was no statistically significant correlation between serum levels of carbamazepine or carbamazepine-10,11-epoxide and the EEG parameters. Our results demonstrate that the degree of EEG change primarily reflects individual susceptibility to carbamazepine and its metabolite during the early stage of carbamazepine exposure and is not dose related.     

EEG changes induced by carbamazepine therapy at rest and during mental processes

The effects of carbamazepine (CBZ) on EEG backgrouund activity have been studied, at rest and during mental processes, in 18 epileptic patients suffering from focal epilepsy and starting antiepileptic treatment for the first time. The EEGs were recorded before and after CBZ therapy, at rest with eyes closed (EC), during blocking reaction (BR), fixation (FIX) and mental arithmetic (MA) tasks, and then evaluated by spectral analysis. All data underwent statistical evaluation utilizing the ANOVA and correlation coefficient. The following parameters were evaluated by spectral analysis. All data underwent statistical evaluation utilizing the ANOVA and correlation coefficient. The following parameters were evaluated: mean absolute and relative power and mean frequency. The results have shown that CBZ induced a significant increase of slow activity at rest with EC, which was represented by delta potentials, and was correlated with CBZ plasma levels, In evaluating the different cortical activation patterns, a decrease of the alpha reactivity was noted during BR and FIX, while a significant increase of beta activity was observed during the performance of all tasks. The rwelationship between the increased beta power, possibly reflecting an increase of cognitive activity for processing information, and the lack of a significant decrease of alpha activity are discussed.Paper presented at the National Congress at Serrento in 1991 and selected by the Editorial Board of the Journal     

EEG and seizure exacerbation induced by carbamazepine in Panayiotopoulos syndrome.

We report on a 4-year 8-month-old boy with Panayiotopoulos syndrome who showed atypical evolution with newly developed absence seizures and EEG exacerbation induced by carbamazepine. Soon after the introduction of carbamazepine, EEGs began to worsen, and finally absence seizures and myoclonic seizures appeared. Immediately after we discontinued carbamazepine, the seizures disappeared and the EEG improved. Carbamazepine may induce unusual electroclinical features, electrophysiologically explained by bilateral synchrony. This case provides more evidence of the close links between Panayiotopoulos syndrome and benign childhood epilepsy with centrotemporal spikes.     

Long-term treatment with carbamazepine affects CSF somatostatin immunoreactivity in epileptic patients.

A number of pharmacological evidence supports the view that somatostatin (SS) may be importantly involved in the seizure susceptibility both in humans and in laboratory animals. In a previous report the Authors have provided the finding that a short-term carbamazepine (CBZ) administration is able to reduce SS-CSF-IR in epileptic patients. The present study has been carried out to investigate whether a long-term treatment with CBZ affects in a similar way SS-IR content in CSF from temporal lobe epileptics (CPS). The results confirm and expand previous evidence suggesting that CBZ lowering effect on CSF-SS-IR may be relevant to its anticonvulsivant action.     

Water intoxication in epileptic patients receiving carbamazepine.

Plasma sodium and osmolality were determined in 80 adult epileptic patients receiving chronic treatment with carbamazepine and in 50 control patients treated with other anticonvulsant drugs. Mean plasma osmolality was significantly lower in the carbamazepine-treated patients but mean plasma sodium did not differ in the two groups. Hyponatraemia was found in five of the carbamazine-treated patients and hypo-osmolality in six. None of the control patients had hyponatraemia and only one had a borderline low osmolality. Three of the 13 patients receiving carbamazepine alone were hyponatraemic. Plasma sodium concentration correlated negatively with both daily carbamazepine dose and serum carbamazepine level. Free water clearance after an oral water load was determined in six patients on carbamazepine alone and in six normal subjects not receiving drug therapy. The capacity of some of the patients to excrete the water load was found to be grossly impaired.     

A quantitative study of daytime sleepiness induced by carbamazepine and add-on vigabatrin in epileptic patients

Introduction – The clinical relevance of daytime sleepiness associated with carbamazepine (CBZ) and vigabatrin (VGB) was objectively assessed by the multiple sleep latency test (MSLT) and nocturnal sleep recordings. Material and methods – Twenty-six patients with partial epilepsy and mean monthly seizure frequency of 4, aged 18 to 48 years, receiving chronic monotherapy with CBZ and subsequent VGB addition for 2 months (14 patients), were compared with a group of healthy subjects. Subjective daytime sleepiness was complained by 13 patients on CBZ monotherapy and 9 patients during VGB add-on treatment. Results – No differences in nocturnal sleep parameters, but significantly shorter daytime sleep latencies at the MSLT, were detected in CBZ-treated patients as compared with healthy controls. Addition of VGB therapy did not further enhance objective daytime sleepiness. Conclusion – Some sleepiness occurs in chronically CBZ-treated epileptic patients, which can be objectively measured by the MSLT, but it is not aggravated by add-on VGB.     

Laser evoked potentials and carbamazepine in epileptic patients.

AIMS OF THE STUDY: Nerve conduction studies have demonstrated that carbamazepine (CBZ), as well as other antiepileptic drugs (AEDs), can affect peripheral nerve conduction; reports on conventional somatosensory evoked potentials and CBZ are controversial. In a previous study, assessing laser-evoked potentials (LEPs) in CBZ-treated patients with idiopathic trigeminal neuralgia, we found that LEPs were dampened even after stimulation of the non-painful side, with a strong correlation between LEP latency and daily CBZ dose. No other study investigated the influence of AEDs on LEPs. In order to clarify the effect of CBZ on LEPs we sought possible LEP changes in epileptic patients taking CBZ. MATERIALS AND METHODS: We studied LEPs after trigeminal and hand CO(2)-laser stimulation in 20 patients with epilepsy taking CBZ and 20 age-matched controls. RESULTS: Although the trigeminal LEP mean latency was slightly longer in epileptic patients (P=0.11), we did not find significant differences between epileptic patients and controls for any LEP data. LEP data did not correlate with the daily CBZ dose, CBZ blood concentration, or duration of therapy (P>0.3). CONCLUSION: The lack of a CBZ-induced dampening of LEPs suggests that small-fibre pathways, compared to large-fibre, might be less susceptible to AED's toxic effect. Although the TN patients in our previous study were older than the epileptic patients in the present study, a possible combined effect induced by drug and age in patients with TN is unlikely because LEP latency is reportedly unaffected by age. The CBZ-induced effect in patients with trigeminal neuralgia is possibly related to pathophysiological changes specific to this disease.     

Temporal changes in c-Fos activation patterns induced by conditioned fear

Mechanisms underlying shock-induced conditioned fear - a paradigm frequently used to model posttraumatic stress disorder, PTSD - are usually studied shortly after shocks. Some of the brain regions relevant to conditioned fear were activated in all the c-Fos studies published so far, but the overlap between the activated regions was small across studies. We hypothesized that discrepant findings were due to dynamic neural changes that followed shocks, and a more consistent picture would emerge if consequences were studied after a longer interval. Therefore, we exposed rats to a single session of footshocks and studied their behavioral and neural responses one and 28 days later. The neuronal activation marker c-Fos was studied in 24 brain regions relevant for conditioned fear, e.g. in subdivisions of the prefrontal cortex, hippocampus, amygdala, hypothalamic defensive system, brainstem monoaminergic nuclei and periaqueductal gray. The intensity of conditioned fear (as shown by the duration of contextual freezing) was similar at the two time-points, but the associated neuronal changes were qualitatively different. Surprisingly, however, Multiple Regression Analyses suggested that conditioned fear-induced changes in neuronal activation patterns predicted the duration of freezing with high accuracy at both time points. We suggest that exposure to electric shocks is followed by a period of plasticity where the mechanisms that sustain conditioned fear undergo qualitative changes. Neuronal changes observed 28 days but not 1 day after shocks were consistent with those observed in human studies performed in PTSD patients.     

Correlations between EEG changes induced by diazepam and the localization of epileptic spikes and seizures

We evaluated the EEG reaction to an intravenous injection of diazepam as an additional tool in difficult localization problems in epilepsy. The normal reaction to diazepam being an increase in beta activity, it was assumed that a poor increase indicated an abnormal region. This method was tested in 21 epileptic patients having chronically implanted intracerebral electrodes. Beta activity before and after injection was quantified by spectral analysis; increases were compared in homologous contralateral channels. In 12 of the 21 cases the area of poorest response to diazepam was identical to that of seizure onset. In 7 cases, there was some overlap between the area of poorest diazepam response and that of seizure onset, but they did not exactly coincide. In two cases there was no overlap between the two areas. Agreement was slightly higher when comparing diazepam response and area of highest interictal spike activity. This procedure is simple and without risk, particularly compared to the thiopental injection which is used for the same purpose. It is helpful in determining abnormal areas when localization information from various diagnostic sources are conflicting. Even when the epileptic focus is well defined, it can point to other poorly functioning areas.     

Impact of levetiracetam add-on therapy on different EEG occipital frequencies in epileptic patients

SummaryThe EEG background activity reflects the functional state of the brain. The established sensitivity of EEG to drug intoxication and in particular to antiepileptic drugs (AEDs) made that EEG has become useful as an objective measure for monitoring chronic AED therapy and in investigation of cognitive functions. Therapy with classical AEDs has become associated with slowing of EEG background rhythm and the EEG changes correlated to changes on cognitive measures. So far, it has not been tested whether the relatively new AED, levetiracetam (LEV) has a detrimental effect on the EEG background frequencies, too.MethodsDuring the time of 6 months 28 patients underwent EEG-recording and neuropsychological testing at the three timepoints: before initiating LEV therapy, after 2 months and again after 4 months after achieving plateau dosing of LEV. EEG background frequency was analysed by using the fast Fourier Transform (FFT).ResultsThe titration and the following treatment with LEV add-on showed no negative effect on any of the measures analysed. In particular it did not lead to the lower peak frequency within the alpha band, it neither decreased the percentage of alpha band nor increase the percentage of theta and delta band. In addition there could be noticed an increase of the percentage of beta band.ConclusionsOur findings demonstrate, that a LEV add-on therapy is not associated with a slowing of the EEG background frequency. This is in accordance with neuropsychological reports of our own lab and others showing that LEV add-on therapy has no negative effects on cognitive functions, either.