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PubMed1989

Personality characteristics and epilepsy.

Patients with a long history of temporal lobe epilepsy or primary generalized epilepsy entered a questionnaire study of personality characteristics, based on a modification of the Bear-Fedio inventory for temporal lobe behavioural syndrome. Psoriasis patients and healthy volunteers served as controls. Four clinical meaningful dimensions of included personality traits were identified: ixoide, ideational, obsessive-compulsive and affective features. Analyses based on the Rasch model approved of all dimensions except for affective features. The epilepsy group obtained the highest scores on all 3 dimensions, healthy volunteers the lowest, while the psoriasis group repeatedly held an intermediate position in all sets of assessment (subjects, interviewers and relatives). A logistic regression analysis showed ixoide features being most important when the entire epilepsy group was compared with other study groups, while the dimension ideational features was significant when the temporal lobe epilepsy group was entered as target group and opposed to primary generalized epilepsy. The intermediate position of the psoriasis group, however, suggests that in addition to the presence of a cerebral dysfunction in the epilepsy group, the mere presence of a chronic disorder with potential social stigmatization influences personality.

Adult↗

PubMed2001

Enhanced inactivation and acceleration of activation of the sodium channel associated with epilepsy in man.

Generalized epilepsy with febrile seizures-plus (GEFS+) is a benign Mendelian syndrome characterized by childhood-onset febrile and afebrile seizures. Three point mutations within two voltage-gated sodium channel genes have been identified so far: in GEFS+ type 1 a mutation in the beta1-subunit gene SCN1B, and in GEFS+ type 2 two mutations within the neuronal alpha-subunit gene SCN1A. Functional expression of the SCN1B and one of the SCN1A mutations revealed defects in fast channel inactivation which are in line with previous findings on myotonia causing mutations in SCN4A, the skeletal muscle sodium channel alpha-subunit gene, all showing an impaired fast inactivation. We now studied the second GEFS+ mutation (T875M in SCN1A), using the highly homologous SCN4A gene (mutation T685M). Unexpectedly, the experiments revealed a pronounced enhancement of both fast and slow inactivation and a defect of channel activation for T685M compared to wild-type channels. Steady-state fast and slow inactivation curves were shifted in the hyperpolarizing direction, entry into slow inactivation was threefold accelerated, recovery from slow inactivation was slowed by threefold and the time course of activation was slightly but significantly accelerated. In contrast to other disease-causing mutations in SCN1A, SCN1B and SCN4A, the only mechanism that could explain hyperexcitability of the cell membrane would be the acceleration of activation. Because the enhancement of slow inactivation was the most obvious alteration in gating found for T685M, this might be the disease-causing mechanism for that mutation. In this case, the occurrence of epileptic seizures could be explained by a decrease of excitability of inhibitory neurons.

Animals↗

PubMed1988

Mono- or polytherapy and the severity of epilepsies.

1. Out of 295 outpatients who were followed up by our staff for longer than 4 years, a total of 196 patients was subjected to this retrospective study. The inclusion criterion was that they had inevitably been placed on polytherapy of two or more anti-epileptic drugs (AEDs). In other words, they had failed to reach monotherapy for some reasons. 2. One of the determinant factors for the success or failure of monotherapy was the type of epilepsies. Namely, primary generalized epilepsy (PGE) was relatively easy to attain by monotherapy regardless of the seizure type, whereas secondary generalized epilepsy (SGE) with combined seizures and secondary partial epilepsy (SPE) with mixed seizures were not infrequently difficult to be placed on a monotherapy regimen. In the latter case, however, an abrupt withdrawal of AEDs was apt to cause an exacerbation of seizures. 3. There were some patients who could reach a complete freedom from seizures as a result of bi- or polytherapy and became socially adaptable and acceptable. They themselves are, if not all, afraid of a possible relapse of seizures produced by a reduction in the number of AEDs hitherto prescribed. In some cases, a family member may refuse monotherapy, or even physicians are reluctant to switch to monotherapy because the patients have experienced status epilepticus in the past.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1996

Generalized absence epilepsy and catalepsy in rats.

Adult WAG/Rij rats are considered adequate genetic models for human generalized absence epilepsy. Rats of this strain of 8, 12, and 18 weeks old and age-matched control Wistar rats were exposed to sound stimulation. After offset of stimulation, all WAG/Rij rats showed cataleptic or even cataplexic reactions, which could persist for up to 20 min. Age effects could be demonstrated. None of the Wistar rats showed cataleptic reactions. Electroencephalographic studies in WAG/Rij rats of 21 weeks showed that spike-wave discharges were abundantly present in the background electroencephalogram prior to sound stimulation. Age-matched Wistar rats had almost no spike-wave discharges. Spike-wave discharges in WAG/Rij rats disappeared during sound stimulation and were then increased compared to the prestimulation and stimulation periods. The electroencephalogram during the cataleptic state was also characterized by the presence of large amplitude 2 Hz waves, interspersed with spike-wave discharges. The data suggest that the cataleptic state can be elicited in genetically epilepsy-prone rats. The youngest WAG/Rij rats showed no spike-wave discharges during the cataleptic state. In all, the data suggest that epilepsy-prone animals are sensitive for catalepsy at an age at which the EEG signs of generalized absence epilepsy are not yet manifest.

Animals↗

PubMed2004

The choice of antiepileptic drugs in newly diagnosed epilepsy: a national French survey.

The choice of an antiepileptic drug (AED) in patients with epilepsy is mainly based on efficacy and safety of each drug. However, these criteria of drug selection should be further evaluated according to the epileptic syndromes, and adjusted to the sex and age of the patient. Unfortunately, very few studies have been conducted based on these latter criteria. We conducted a survey on the management of epilepsy treatment in adults. This survey was undertaken in France, and led to the establishment of a French consensus on antiepileptic drug treatment in adult patients with newly diagnosed epilepsy. Patients were grouped into 18 categories according to the epileptic syndrome (absence epilepsy, juvenile myoclonic epilepsy, undetermined idiopathic generalized epilepsy, symptomatic or cryptogenic partial epilepsy and unclassified epilepsy), and to the patient's gender and age. Our survey suggests that there is a consensus among French epileptologists for the choice of AEDs, mainly based on the epilepsy syndrome. Gender also plays a crucial role. Sodium valproate and lamotrigine are the two drugs of choice for generalized epilepsies, as well as for undetermined epilepsies. Lamotrigine is often prefered for women of childbearing age. First line AEDs in partial epilepsy are carbamazepine (particularly for men), lamotrigine (particularly for women), and gabapentin (in the elderly). In cases of failure and/or intolerance to one of these AED, the principal alternatives are oxcarbazepine, sodium valproate and topiramate.

Adolescent↗

PubMed1999

Incidence of epileptic syndromes in Rochester, Minnesota: 1980-1984.

PURPOSE: To determine the incidence and the distribution of epileptic syndromes in a well-defined population. METHODS: By using the records-linkage system of the Rochester Epidemiology Project, we screened all the residents of Rochester, Minnesota, who received a diagnosis of seizures, convulsions, or epilepsy from 1980 through 1984. One hundred fifty-seven residents with incident epilepsy (recurrent unprovoked seizures) were classified by using the International League Against Epilepsy (ILAE) Classification of the Epilepsies and Epileptic Syndromes. Residents with special syndromes were excluded. With a pretested algorithm, patients were classified at three levels of specification: major syndromic groups (e.g., localization-related syndromes), syndromic subgroups (e.g., idiopathic epilepsy with age-related onset), and whenever possible, individual syndromes. RESULTS: All but one patient were classified into major syndromic groups and subgroups. The annual age-adjusted incidence per 100,000 population was 52.3 cases (34.9 for localization-related epilepsies; 7.7 for generalized epilepsies; 9.7 for undetermined epilepsies). Incidence was 0.2 for idiopathic, 17.2 for cryptogenic, 17.5 for symptomatic localization-related epilepsies, 3.7 for idiopathic, 1.7 for symptomatic or cryptogenic (age-related), and 2.3 for symptomatic (non age-related) generalized epilepsies. CONCLUSIONS: With the exception of idiopathic epilepsies, the incidence of the major syndromic categories in our study was higher than that provided by previous population-based studies.

Adolescent↗

PubMed1975

Effect of PGF2 alpha and 15(S)-15-methyl PGE2 methyl ester on feline generalized penicillin epilepsy.

The effect of PGF2alpha and 15(S)-15-methyl PGE2 methyl ester on transient generalized epilepsy in the cat induced by penicillin was examined. Epileptic activity before and after administration of the prostaglandins by several routes was determined from continuous EEG recordings and expressed in epileptic bursts per min. The PGE2 analogue given in single non-toxic doses (1.6-3 mug/kg) by intramuscular or intravenous routes at the peak of epileptic activity significantly reduced epileptic activity for up to four hours. Subcutaneous administration was less effective. PG2alpha given by the intramuscular route (0.3 mg/kg) also markedly reduced the number of epileptic bursts. Increasing the dosage 4-fold almost completely suppressed epileptic activity. Intracarotid infusion of PGF2alpha for one hour (10 mug/min) almost abolished all epileptic activity. Neither prostaglandin given in non-toxic doses induced EEG abnormalities in non-epileptic cats. Toxic doses of the E2 analogue (greater than 16 mug/kg) caused bilaterally synchronous high voltage slow wave activity. It is concluded that these prostaglandins reduce penicillin epilepsy in the cat. The findings are consistent with either a direct excitatory action on neurones of the medial reticular formation or anatagonism of the depressant action of norepinephrine on Purkinje cells.

Animals↗

PubMed2001

A pharmacoepidemiologic study of factors influencing the outcome of treatment with lamotrigine in chronic epilepsy.

PURPOSE: To identify prognostic factors for freedom from seizures and long-term retention of treatment in patients receiving lamotrigine (LTG). METHODS: A multicenter, retrospective, case record study of 1,050 patients with chronic epilepsy was carried out. Logistic regression and Cox regression analyses were used to identify clinical features associated with freedom from seizures and retention of treatment, respectively. Long-term retention rates of LTG therapy were estimated using Kaplan-Meier survival analysis. RESULTS: The 1,050 patients with chronic epilepsy were included in the study. Patients with generalized epilepsy (p = 0.01), who were not receiving carbamazepine (CBZ; p = 0.02) were more likely to become seizure-free. Sixty percent of patients continued on LTG therapy >1 year and estimated retention at 8 years was 38%. Patients with generalized epilepsy (p = 0.002), patients receiving concurrent sodium valproate (VPA; p < 0.0001), those not previously exposed to gabapentin and vigabatrin (p < 0.0001), and those in whom the starting dose was lower (p < 0.0012), were more likely to remain on long-term treatment with LTG. The relationships with exposure to other antiepileptic drugs remained significant in patients with focal and with generalized epilepsy when considered separately. CONCLUSIONS: The best results from LTG treatment in terms of freedom from seizures and long-term retention of treatment were obtained in patients with generalized epilepsy. Retention of treatment was enhanced by VPA not only in generalized but also in focal epilepsy. The importance of a low starting dose of LTG was again confirmed. The apparent negative effect of CBZ in patients taking LTG merits further investigation.

Anticonvulsants↗

PubMed1981

The effects of transient functional depression of the thalamus on spindles and on bilateral synchronous epileptic discharges of feline generalized penicillin epilepsy.

A transient functional depression of thalamic activity (TFDTA) was induced in acute experiments in cats by the microinjection of 25% KCl into the thalamus. Spontaneous and evoked thalamic electrical activity was markedly depressed at the site of KCl microinjection. Spread of this depression to other thalamic areas often occurred, mainly when KCl was injected into the midline thalamus. In normal cats both spontaneous and evoked cortical spindle bursts as well as other evoked thalamocortical responses were reduced or abolished during the KCl-induced TFDTA. The generalized spike-and-wave discharges of feline generalized epilepsy were also suppressed for the duration of TFDTA, while incidental focal cortical interictal and ictal epileptic discharges, as well as generalized tonic-clonic seizure discharge, remained unaffected. The same effects were observed in animals with lesions of the mesencephalic reticular formation, indicating that the suppression of spindles and spike-and-wave discharges cannot be attributed to a release of the activity of the reticular formation by the TFDTA. An unexplained occurrence of generalized tonic-clonic EEG seizure was observed in most cases late after thalamic KCl microinjection, usually after the spike-and-wave discharges had recovered. These data are consistent with the hypothesis that the spontaneous bilaterally synchronous epileptic bursts of feline generalized penicillin epilepsy are not only closely related to spindles but are crucially dependent on thalamic inputs to the cerebral cortex.

Animals↗

PubMed2005

Management of epilepsy in general practice patients.

The BEACH program, a continuous national study of general practice activity in Australia, gives us an overview of consultations in general practice involving the management of epilepsy. Participating general practitioners recorded the problem as 'epilepsy' in 90% of cases, while 'grand mal' was specified at about 4% of encounters and 'temporal lobe' and 'petit mal' were each specified at about 1% of encounters.

Adolescent↗

PubMed1975

Response of generalized penicillin epilepsy in the cat to ethosuximide and diphenylhydantoin.

The effects of ethosuximide and diphenylhydantoin sodium on feline generalized penicillin epilepsy, a model of human generalized corticoreticular (centreccephalic) epilepsy, were significantly reduced following administration of ethosuximide with plasma levels of 60 mug per milliliter, and there was a linear correlation between the plasma level and antiephilepileptic effect (p less than 0.01). Diphenylhydantoin produced a lesser reduction in epileptic activity, and there was no correlation between the plasma level and effect. Four cats that received both drugs successively responded well to ethosuximide, while only two responded to diphenylhdantoin. The good response to ethosuximide is in accord with clinical experience in human generalized corticoreticular epilepsy.

Animals↗

PubMed1977

Profile of epilepsy in a developing country: a study of 1,000 patients based on the international classification.

The present prospective study undertaken in a specialized neurological center of a developing country deals with 1,000 epileptic patients classified in accordance with the International Classification. Eighty-one percent of the patients could be classified, with a lower incidence in the younger age group. Partial epilepsy was found to be far more common than generalized epilepsy (80% versus 20%). Primary generalized epilepsy was seen in 15% and secondary generalized in 5%. Partial epilepsy with elementary symptomatology was seen in 58% and complex symptomatology in 7%. Secondarily generalized seizures were seen in the remaining 15%. Primary generalized epilepsy and partial epilepsy with complex symptomatology were more common in adults. Secondary generalized epilepsy and partial epilepsy with secondarily generalized seizures were more common in children. Partial epilepsy with elementary symptomatology, however, did not vary significantly with age. The higher incidence of partial epilepsy in our patients, compared to the West, could be due to greater frequency of CNS infections and birth injuries, which are common childhood hazards in the developing countries.

Adult↗

PubMed1999

Generalized convulsive epilepsy: possible mechanisms.

Neuronal mechanisms underlying focal convulsions and secondary generalized convulsions continue to be intensively investigated and many important pathophysiological processes are now recognized. Our understanding of primary generalized convulsions remains limited in spite of a variety of approaches. While there are well known clinical situations offering insights into some aspects of the pathophysiology, studies in animal models of generalized convulsions offer a deeper understanding of some of the processes likely to be occurring. Animal studies have indicated that generalized convulsive epilepsies are likely to be comprised of several types of convulsion and that these arise from more than one neuronal network. In particular, the cortex and brain stem can interact in various ways to lead to convulsions and may even act independently. Pharmacological agents can produce specific changes in the excitability of neurons and cause generalized convulsions, so providing models of the possible neurophysiological defects in humans. Based on electrophysiological recordings of generalized convulsions in these animal models, we also suggest that the convulsion involves subcortical mechanisms and raise the idea that primary generalized convulsive epilepsy arises out of intensified (synchronized) normal brain rhythms. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗

PubMed1983

[Monotherapy with sodium valproate in generalized primary epilepsy. 2d phase: Study of long-term efficacy and tolerance].

From the analysis of 115 cases of primary generalized epilepsies treated for a mean duration of 43 months with sodium valproate as sole therapy, it appears that: the mean effective daily dosage is 21 mg/kg; the efficacy of valproate proved excellent in 82.6% of cases (seizures fully controlled: 74%, seizures occurring exceptionally: 9%); a loss of activity was never observed; in these circumstances of prolonged administration of the drug, no signs of major intolerance were seen; side-effects occurred in 29% of cases, including 20% long-term effects (weight gain, essential tremor); 64 series of laboratory tests including 15 parameters made it possible to evaluate the hematological, hepatic and pancreatic tolerance of valproate: the majority of the tests were normal. The authors believe that during long-term therapy with valproate, monitoring does not need to include the routine performance of liver function tests, but that it would be more advisable, should a suggestive clinical sign be noted, to investigate the platelet count, coagulation (partial activated thromboplastin time) and protein synthesis (fibrinogen).

Adult↗

PubMed1993

Atrophy of mesial structures in patients with temporal lobe epilepsy: cause or consequence of repeated seizures?

We studied 70 epileptic patients by using magnetic resonance imaging volumetric measurements of amygdala (AM) and hippocampal formation (HF). Fifty patients presented with intractable temporal lobe epilepsy (TLE), 10 patients had focal extratemporal lobe epilepsy, and 10 had generalized epilepsy. In 91% of the 45 TLE patients without foreign tissue lesions, there was significant smallness of the AM and/or HF coinciding with the side of electroencephalographic seizure onset. No significant smallness or asymmetry was demonstrated in patients with focal extratemporal or generalized epilepsy. We performed a linear regression analysis, plotting the number of years of recurrent seizures and the estimated seizure frequency against the volumes of the AM and HF. There was no correlation between either of these two parameters and AM or HF volume (p > 0.9). There was also no correlation between the patient's age and volumetric measurements of AM or HF, nor did these measurements correlate with the occurrence of generalized seizures. On the other hand, patients with antecedent prolonged febrile convulsions in early childhood had significantly smaller AM and HF, compared with those without such a history (p < 0.001). The findings indicate that repeated seizures or longer duration of epilepsy do not cause increased atrophy of AM or HF that is measurable by volumetric magnetic resonance imaging.

Adolescent↗

PubMed1981

[Individualization of so-called benign and functional epilepsy at different ages. Appraisal of variations corresponding the predisposition for epilepsy at these ages].

The different types of epilepsy encountered during the various phases of life are presented and the distinction is made between benign and, essentially if not exclusively, functional epilepsy related to a genetically-transmitted predisposition to epilepsy: (1) the primary generalized epilepsies and (2) the benign partial epilepsies with functional foci. In the case of primary generalized epilepsy, seizures are the result of a discharge, generalized from the onset, of the entire cortex in individuals genetically predisposed to epilepsy. The seizures present (1) in older children, adolescents and young adults, the well-known characteristics of Petit Mal and/or Grand Mal; (2) in neonates, infants and young children, a different type of generalized (or hemigeneralized) seizures, the semeiology of which remains unclear. In the case of benign partial epilepsy, the seizures result from an epileptic discharge in a cortical area having a low convulsant threshold in patients genetically predisposed to epilepsy. The semeiology of the seizures varies as a function of the patient's age and the site of the epileptic focus: -in neonates: benign partial epilepsy wih an erratic EEG focus, e.g. 'Fifth day seizures'; -in infants: 'cryptogenic' benign partial epilepsy, which remains poorly defined; -in children: (a) benign partial epilepsy with nocturnal motor seizures and a central EEG focus; (b) benign partial epilepsy with affective seizures and a temporal focus; (c) benign partial epilepsy with visual seizures (often coupled with signs of basilar migraine) and an occipital focus; -in adolescents: benign partial motor epilepsy (often versive) often without an interictal EEG focus or with generalized spike-waves; benign partial epilepsies do not occur after adolescence.

Adolescent↗

PubMed2006

[Clinical observation on catgut implantation at acupoint for treatment of general paroxysmal epilepsy].

OBJECTIVE: To search for an effective method for treatment of general paroxysmal epilepsy. METHODS: One hundred cases were randomly divided into a treatment group of 50 cases treated with catgut implantation at Dazhui (GV 14), Jinsuo (GV 8), Fenglong (ST 40), etc., and a control group of 50 cases treated with oral administration of sodium valproate. RESULTS: The scores for epilepsy after treatment significantly improved in the both groups (P<0.05); the total effective rate was 94.0% in the treatment group and 82.0% in the control group with a significant difference between the two groups (P<0.05). CONCLUSION: Catgut implantation at acupoint has a definite therapeutic effect on general paroxysmal epilepsy with no adverse effect.

Acupuncture Points↗

PubMed1986

[Role of the thalamus in the physiopathology of epilepsy].

Early hypotheses on the origin of primary generalized epilepsy suggested a determinant role for the "centrencephalon" in the triggering of discharges of generalized spike-waves (GSW) and tonic-clonic crises (TCC). It was demonstrated in this respect that bilateral cortical spike-wave discharges at 3 c/sec were obtained by electrical stimulation of intralaminar nuclei in the rat. The role of the thalamus in the genesis of GSW and TCC was subsequently demonstrated in several experimental models. However, the thalamus is apparently not involved in the genesis of EEG manifestations of generalized epilepsy and most authors agree that the latter are of cortical origin since a) with or without cardiazol, generalized seizures may occur after ablation of cat thalamus; b) in the cat diffuse cortical application of dilute penicillin can reproduce signs of generalized epilepsy observed after systemic injection of penicillin to this animal; c) finally paroxysmal discharges which appear in subcortical structures in the photosensitive baboon are always preceded by frontal cortical spike-waves; similarly intermittent light stimulation-provoked TCC always arise from the frontal cortex and furthermore hemispheric synchronization of attacks disappears after callosotomy. These findings indicate that the origin of GSW and TCC, is not in the thalamus but that the latter nevertheless plays a role in their elaboration.

Animals↗