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PubMedDate not supplied

Cerebellar nuclear stimulation in generalized penicillin epilepsy.

Comparison was made of the effectiveness of cerebellar cortical and nuclear stimulation in reducing paroxysmal activity induced in cats by parenteral penicillin administration. Vermal cortical and fastigial nuclear stimulation at high frequencies (100 Hz) were both effective in reducing the number and duration of paroxysmal events while the effects of dentate nucleus stimulation were found to be more variable. It was suggested that effective seizure inhibition appeared to be associated with increased fastigial output and resultant reticular excitation.

Animals↗
PubMedDate not supplied

Neuronal firing patterns during generalized penicillin epilepsy in the awake cat.

Single unit activity was recorded in the neocortex of awake cats during spontaneous spike wave discharges. Ongoing activity was interrupted during paroxysmal events and was replaced by (1) bursts of action potentials coincident with the EEG spike and cessation of firing during the wave, or (2) cessation of firing for the duration of the paroxysm. Other units which displayed little or no background activity were recruited to fire during the EEG spike. Surface cerebellar stimulation at high frequencies led to decreased neuronal activity while single pulse shocks resulted in short latency activation. These results were compared to studies of spike wave activity elicited by electrical stimulation.

Animals↗
PubMed1998

Mechanisms of generalized absence epilepsy.

Absence seizures represent bilaterally synchronous burst-firing of an ensemble of reciprocally connected neuronal populations located in the thalamus and neocortex. Recent studies demonstrate that neurons in the reticular thalamic nucleus (nRt), thalamic relay neurons (RNs), and neocortical pyramidal cells comprise a circuit that sustains the thalamocortical oscillatory burst-firing of absence seizures. Recent studies have focused on three intrinsic neuronal mechanisms that increase the likelihood of thalamocortical oscillations. The first mechanism involves T-currents elicited by activating the T-type calcium channel, which appear to trigger sustained burst-firing of thalamic neurons during absence seizures. A second intrinsic mechanism is GABA B receptors which can elicit longstanding hyperpolarization in thalamic neurons required to 'prime' T-channels for sustained burst-firing. A third mechanism involves the ability of GABA A receptors, located on nRt neurons, to mediate recurrent inhibition. Enhanced activation of GABA A receptors on nRt neurons decreases the pacemaking capacity of these cells, therefore decreasing the likelihood of generating absence seizures. Cholinergic mechanisms through modulating cortical excitability and excitatory amino acid mediated mechanisms through depolarizing thalamic neurons also play a role in absence seizures.

Animals↗
PubMed2000

Physiological basis: how NREM sleep components can promote and REM sleep components can suppress seizure discharge propagation.

OBJECTIVES: To describe how the neural generators of different sleep components can provoke seizure discharge propagation during NREM sleep and can suppress it during REM sleep. METHODS: Experimental manipulations of discrete physiological components were conducted in feline epilepsy models (n=64), mostly in the systemic penicillin epilepsy model of primary generalized epilepsy and the amygdala kindling model of the localization-related seizure disorder, temporal lobe epilepsy. Procedures included seizure induction as well as quantifying norepinephrine concentrations (microdialysis) and the sleep-waking state distribution of seizures before and after lesions, systemic and localized drug administration and/or photic stimulation. RESULTS: (1) Neural generators of synchronous EEG oscillations, including tonic background slow waves and phasic 'arousal' events (sleep EEG transients such as sleep spindles, k-complexes), can combine to promote electrographic seizure propagation during NREM and drowsiness; anti-gravity muscle tone permits seizure-related movement. (2) Neural generators of asynchronous neuronal discharge patterns can reduce electrographic seizures during alert waking and REM sleep; skeletal motor paralysis blocks seizure-related movement during REM. (3) Etiology of the seizure disorder can interact with sleep and arousal mechanisms to determine sleep-waking state distribution of interictal and ictal events. CONCLUSIONS: Differential effects of NREM versus REM sleep components on seizure discharge propagation are to some extent non-specific and in other ways specific to seizure etiology.

Animals↗
PubMed2006

Single-channel properties of human NaV1.1 and mechanism of channel dysfunction in SCN1A-associated epilepsy.

Mutations in genes encoding neuronal voltage-gated sodium channel subunits have been linked to inherited forms of epilepsy. The majority of mutations (>100) associated with generalized epilepsy with febrile seizures plus (GEFS+) and severe myoclonic epilepsy of infancy (SMEI) occur in SCN1A encoding the NaV1.1 neuronal sodium channel alpha-subunit. Previous studies demonstrated functional heterogeneity among mutant SCN1A channels, revealing a complex relationship between clinical and biophysical phenotypes. To further understand the mechanisms responsible for mutant SCN1A behavior, we performed a comprehensive analysis of the single-channel properties of heterologously expressed recombinant WT-SCN1A channels. Based on these data, we then determined the mechanisms for dysfunction of two GEFS+-associated mutations (R1648H, R1657C) both affecting the S4 segment of domain 4. WT-SCN1A has a slope conductance (17 pS) similar to channels found in native mammalian neurons. The mean open time is approximately 0.3 ms in the -30 to -10 mV range. The R1648H mutant, previously shown to display persistent sodium current in whole-cell recordings, exhibited similar slope conductance but had an increased probability of late reopening and a subfraction of channels with prolonged open times. We did not observe bursting behavior and found no evidence for a gating mode shift to explain the increased persistent current caused by R1648H. Cells expressing R1657C exhibited conductance, open probability, mean open time, and latency to first opening similar to WT channels but reduced whole-cell current density, suggesting decreased number of functional channels at the plasma membrane. In summary, our findings define single-channel properties for WT-SCN1A, detail the functional phenotypes for two human epilepsy-associated sodium channel mutants, and clarify the mechanism for increased persistent sodium current induced by the R1648H allele.

Alleles↗
PubMed2004

Statistics on deliveries of mothers with epilepsy at Yokohama City University Hospital.

PURPOSE: To survey and summarize the treatment of pregnant women with epilepsy and to obtain data for the improvement of daily treatment regimens. METHODS: We reviewed medical records of 36 deliveries of 25 mothers with epilepsy at Yokohama City University Hospital from September 1991 to December 2000 and statistically compared the differences in drug-taking profiles, complications during pregnancy, types of delivery, and complications at delivery between the epilepsy group and a control group (656 total deliveries after 22 weeks except for epilepsy cases in 1991 and 1992 at Yokohama City University Hospital). RESULTS: Of the 25 mothers with epilepsy, three with idiopathic generalized epilepsy, 12 were symptomatic for partial epilepsy. Their mean age at delivery was 29.0 years. The mean age at onset of epilepsy was 13.9 years. Of the 36 pregnancies, 30 (83.3%) cases continued antiepileptic drug (AED) taking throughout the pregnancies; 23 (63.9%) cases received monotherapy. Phenobarbital was the most frequently used drug in monotherapies. Seven (19.4%) cases received polytherapy. Seven (19.4%) patients experienced epileptic seizures during pregnancy. One case showed a low serum AED level. No statistically significant difference was found in complications during pregnancy, types of delivery, or complications at delivery, excluding abnormal rotation in the birth canal. Congenital malformation (cleft lip with palate) was observed in one (2.9%) case. The mother was 39 years old at delivery and had myoma uteri. Onset of epilepsy was at 14 years. She had been taking three kinds of AEDs: 1,400 mg/day of sodium valproate (VPA), 1.5 mg/day of clonazepam (CZP), and 200 mg/day of zonisamide (ZNS). Serum concentrations at pregnancy week 10 were 85.3 microg/ml VPA, 18.1 microg/L CZP, and 10.5 microg/ml ZNS. She also had been taking folic acid, 5 mg/day, but the serum concentration was not measured. CONCLUSIONS: The method of treatment and the management of pregnancy were left to the discretion of each doctor. However, in most cases, monotherapy was selected; and the frequency of complications was not significantly different from that of the control group, excluding the frequency of abnormal rotation in the birth canal. However, we could have been more proactive in calculating the risks of pregnancy for women with epilepsy and adjusted treatment in anticipation of a planned pregnancy, before the patient actually became pregnant. Additionally, a closer working relationship between the obstetrician and the physician who treats the epilepsy would seem to be a further requirement for the patient's well-being, as well as her child's, during pregnancy.

Abnormalities, Drug-Induced↗
PubMed1981

Seizures in the newborn and young infants.

The electro-clinical features of neonatal seizures were described. Although they were usually secondary to the underlying pathological process, there were a few cases of benign familial convulsions which seemed to be dominantly inherited. In the new born, clinical seizures occurred mainly in active-REM sleep in contrast to those in the older children and adults. Atypical seizures were also seen in young infants, although less frequently than in the newborn. There were a considerable number of epilepsies beginning in the first year of life associated with a favorable prognosis. Unclassified epilepsies manifesting as brief generalized motor seizures with normal interictal EEGs showed the most favorable outlook, while infantile spasms and other secondary generalized epilepsies had the worst outcome. Partial seizures were intermediate between the above two.

Child, Preschool↗
PubMed2000

Cerebral and cerebellar volume reduction in children with intractable epilepsy.

PURPOSE: Adult epilepsy studies have demonstrated cerebral and cerebellar volume reduction beyond the epileptogenic zone, correlating this with an inferior surgical outcome. We determined whether brain volumes were reduced in childhood epilepsy and the significance of this. METHODS: Cerebral, cerebellar, and hippocampal volumes were measured by quantitative magnetic resonance imaging on 112 children (ages 4-18) with epilepsy syndrome determined by video-EEG telemetry. Eighty-seven had partial epilepsy and 25 had generalized epilepsy or indeterminate syndrome. Normative volumes were obtained from 44 child controls from the community. RESULTS: A significant reduction in cerebral (12.6%) and cerebellar (7.9%) volume was present in the epilepsy group compared with controls. Analysis of subgroups revealed that cerebral volume was significantly decreased in frontal lobe and nonlocalized partial epilepsies. The mean hippocampal ratio of 0.73 for mesial temporal lobe epilepsy was significantly less than for all other syndromes and controls. There was no difference in the rate of hippocampal volume reduction between syndromes. There was a significant correlation between IQ and cerebral and cerebellar volume, but not duration or age of onset of epilepsy. CONCLUSIONS: Cerebral and cerebellar volume reduction is common in intractable epilepsy syndromes of childhood. These cross-sectional data suggest that brain volume reduction is present at epilepsy onset and is not a result of intractable seizures. Hippocampal asymmetry is more sensitive than volume reduction as a marker for mesial temporal lobe epilepsy, but neither measure is specific.

Adolescent↗
PubMed2006

Role of valproate across the ages. Treatment of epilepsy in adults.

A workshop was held in Göteborg in June 2005 to discuss the place of valproate in treating adult epilepsies. Consensus positions were developed on the epilepsy types for which the drug is most suitable and the use of valproate in women of child-bearing age, in men and in patients with psychiatric comorbidity. Valproate was considered to be effective across a broad variety of epilepsy syndromes and seizure types and should be considered a suitable choice for first-line monotherapy of juvenile myoclonic epilepsy and other idiopathic generalized epilepsies. The use of valproate by women of child-bearing age is associated with potential harm to the foetus. A conservative approach to treatment is recommended in these patients whereby alternative antiepileptic drugs should be proposed to women planning pregnancies wherever satisfactory seizure control can be thereby maintained. In cases where valproate is used during pregnancy, either because the pregnancy was unplanned or because alternative treatment options of equivalent efficacy are unavailable, appropriate counselling, precautionary measures and monitoring should be provided. The evidence for an impact of valproate on male reproductive health is equivocal and considerations of male fertility should not be taken into account in deciding whether to prescribe valproate to men. Valproate can be proposed safely to patients with comorbid psychiatric disease or underlying psychiatric vulnerability.

Adult↗
PubMed1981

Dopaminergic mechanism in generalized photosensitive epilepsy.

Apomorphine, a dopamine receptor agonist, blocked epileptic photosensitivity in patients with primary corticoreticular epilepsy. This effect was not modified by naloxone, a narcotic antagonist, suggesting that apomorphine acts on cerebral dopaminergic receptors. Apomorphine did not block spontaneous spike-and-wave discharges in patients with nonphotosensitive primary corticoreticular epilepsy. The different actions of apomorphine on spontaneous and photically induced spike-and-wave activity suggest that there is a selective dopaminergic mechanism in human epileptic photosensitivity.

Adolescent↗
PubMed1998

Centrotemporal spikes in families with rolandic epilepsy: linkage to chromosome 15q14.

OBJECTIVE: To localize a gene predisposing to benign epilepsy of childhood with centrotemporal spikes (BECTS). BACKGROUND: BECTS, or rolandic epilepsy, is the most prevalent idiopathic epilepsy syndrome in childhood. Functional relevant defects in the alpha 4 subunit of the neuronal nicotinic acetylcholine receptor (AChR) have been demonstrated in autosomal dominant nocturnal frontal lobe epilepsy, which, like BECTS, is an idiopathic partial epilepsy. METHODS: A DNA linkage study was conducted screening all chromosomal regions known to harbor neuronal nicotinic AChR subunit genes. Twenty-two nuclear families with BECTS were analyzed. RESULTS: In an "affected-only" study, best p values and lod scores were reached between D15S165 and D15S1010 on chromosome 15q14. In multipoint nonparametric linkage analysis a nominal p value of 0.000494 was calculated by GENEHUNTER. Best parametric results were obtained under an autosomal recessive model with heterogeneity (multipoint lod score 3.56 with 70% of families linked to the locus). These markers are localized in direct vicinity to the alpha 7 subunit gene of the AChR. CONCLUSIONS: We found evidence for linkage of BECTS to a region on chromosome 15q14. Either the alpha 7 AChR subunit gene or a closely linked gene are implicated in pedigrees with BECTS. The disorder is genetically heterogeneous. Surprisingly, the same chromosomal area has been reported to be linked to the phenotype in families with an auditory neurophysiologic deficit as well as in families with juvenile myoclonic epilepsy, another idiopathic but generalized epilepsy syndrome.

Adolescent↗
PubMed2000

[Photogenic epilepsy].

INTRODUCTION: The commonest reflex seizures are those induced by visual stimuli, and amongst these, those provoked by intermittent luminous stimulus. DEVELOPMENT: A directed anamnesis and suitable intermittent light stimulation are important during electroencephalographic studies for the confirmation of the diagnosis of photosensitive epilepsy. The photogenic epilepsies, that is those in which all the epileptic seizures are provoked by visual stimuli, form a small group of epilepsies within the idiopathic generalized epilepsies with their onset during adolescence. These seizures have had great social impact, since media diffusion of the possibility of their appearance whilst watching television or playing video games. CONCLUSION: The correct diagnosis and preventive measures, together with the correct anti-epileptic treatment are in favour of a good prognosis in the great majority of patients.

Adolescent↗