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Childhood febrile convulsions--which factors determine the subsequent epilepsy syndrome? A retrospective study.

To analyze the spectrum of epilepsy syndromes which follow childhood febrile convulsions (FC) and to examine whether retrospective analysis of clinical features of the FC enables discrimination of patients who develop temporal lobe epilepsy (TLE) from those who develop generalized epilepsy (GE). One hundred and thirteen patients with epilepsy and antecedent FC were retrospectively analyzed. We inquired in detail about the clinical characteristics of FC (age, duration, number, focal symptoms) as well as family history, birth history, neurological status, and psychomotor development before onset of FC. Forty five (39.8%) patients had TLE, 41 (36.6%) GE, and 27 (23.9%) had extratemporal epilepsy (ETE). Patients with TLE had a significantly longer duration of FC (P< or =0.001), more often focal features (P< or =0.001), and febrile status epilepticus (P< or =0.001) than patients with GE. Age at FC, Number of FC, family history, birth history and neurological status at FC did not differ between groups. A stepwise discriminant model allowed correct assignment after cross validation in 84.2% to TLE and in 100% to GE. A broad spectrum of epilepsy syndromes follow FC. We found a strong association of prolonged and focal FC with later development of TLE. Short generalized FC were associated with GE.

Adolescent↗

[Epilepsy and Szondi test].

After having briefly recalled the different studies of epilepsy done on the basis of the Szondi test, the author proposes to study the drive structure of three groups of epileptics (19 cases of primary generalized epilepsy, 18 cases of partial temporal lobe epilepsy, 31 cases of partial non-temporal epilepsy) with the purpose of finding possible differences in psychological drive among the three groups and, at the same time, evaluating the test's capacity for discrimination by using the statistical method. The three groups show the same type of profile generally characterized by an extreme need for acceptance and affection (h + !, C- + !) counteracted by a strong repression (hy - !, k -) resulting in agressiveness (s + !). However, statistical analysis (chi square test), the drive formula, the drive class and the EKP showed that, beyond this shared area, there are differences among the three groups. The author then attempts to sort out the meaning of these differences. Finally, based on certain passages from Szondi as well as the test results, the author puts forward an hypothesis linking the psychological drive problematic in primary generalized epilepsies to a very early disturbance in the history of the individual's psychic development, the origins of which would go back to a split in the unity between mother and child. On the other hand, drive disturbances in partial epilepsies would be considered secondary to the illness.

Adolescent↗

Remission of epilepsy: results from the National General Practice Study of Epilepsy.

Remission of seizures is a crucial measure of outcome in epilepsy. The National General Practice Study of Epilepsy (NGPSE) aimed to investigate the remission of patients with epilepsy and the effect of various factors on the likelihood of remission. The NGPSE is a prospective population-based study free from major selection bias. We enrolled 1091 patients with newly diagnosed or suspected epilepsy who attended one of 275 general practices throughout the UK between 1984 and 1987. Remission was analysed in those patients who were classified after 6 months as having definite epilepsy (n = 564) or possible epilepsy (n = 228). After 9 years from the index seizure, 86% (95% CI 81-90) of patients with definite epilepsy had achieved a remission of 3 years and 68% (61-75) a remission of 5 years. For the complete cohort, including those with possible epilepsy, the remission rates at 9 years were 87% (83-91) for 3-year remission and 71% (65-77) for 5-year remission. The proportion of patients with definite epilepsy who were still in remission at 9 years' follow-up (terminal remission) was 68% (62-74) for 3-year and 54% (48-60) for 5-year remission. 61% (56-68) of patients with idiopathic seizures and 61% (46-75) of those with remote symptomatic epilepsy had achieved 5-year remission by 9 years. Overall, age and seizure type had little effect on the chances of achieving remission. This study confirms the good outcome for seizure control in the majority of patients.

Anticonvulsants↗

Small ventricles detected by CT-scanning in epileptic patients.

Relatively young 119 cases of generalized epilepsy and 99 controls of an identical age were selected. The bicaudate CVI was measured and the results were as follows: 1) In our cases, the mean of bicaudate CVI showed a smaller value than those of Hahn's in both epilepsy and control groups. 2) When the value of bicaudate CVI was set up below the point of 8.5 as "excessively small ventricle," the incidence rate of "excessively small ventricle" was 9% in the control group and 31% in the epilepsy group. The data showed higher incidences of small ventricles in the epilepsy group, and that the younger females have a tendency to have higher incidences of small ventricles. 3) To make clear the reason for the higher incidences of small ventricles in epilepsy, the small ventricle group and the non-small ventricle group in epilepsy were compared with each other from the points of the clinical course, EEG findings and frequency of attacks. No correlation or difference between them was found. Further investigation will be needed to make clear the etiology of small ventricles in epilepsy. However, it could be said at the present stage that not so many atrophic changes were observed in the younger patients of generalized epilepsy.

Adolescent↗

Face memory in MRI-positive and MRI-negative temporal lobe epilepsy.

PURPOSE: Effects of MRI-positive (MRI(+)) as compared to MRI-negative (MRI(-)) temporal lobe epilepsy (TLE) on face memory are not yet known. METHODS: We studied 24 MRI(-) (11 right/13 left) and 20 MRI(+) (13 right/7 left) TLE patients, 12 generalized epilepsy patients, and 12 healthy subjects undergoing diagnostic workup with 24-72-h Video-EEG-monitoring. Twenty faces were shown, and had to be recognized from 40 faces immediately and after a 24-h delay. RESULTS: MRI(+) and MRI(-) right TLE (RTLE) patients showed deficits in face recognition compared to controls or generalized epilepsy, consistent with right temporal lobe dominance for face recognition. MRI(+) RTLE patients had deficits in both immediate and delayed recognition, while MRI(-) RTLE patients showed delayed recognition deficits only. The RTLE groups showed comparable delayed recognition deficits. Separate analyses in which the MRI(+) group included patients with hippocampal sclerosis only, did not alter results. Furthermore, MRI(-) RTLE had a worse delayed recognition than MRI(-) left TLE (LTLE). On the other hand, MRI(+) RTLE did not differ from MRI(+) LTLE in delayed recognition. Combining MRI(-) and MRI(+) TLE groups, we found differences between RTLE and LTLE in delayed, but not immediate face recognition. CONCLUSIONS: Our results suggest that a delayed recognition condition might be superior to immediate recognition tests in detecting face memory deficits in MRI(-) RTLE patients. This might explain why former studies in preoperative patients did not observe an immediate face recognition dominance of the right temporal lobe when combining MRI(-) and MRI(+) TLE patients. Our data further point to an important role of the right mesial temporal region in face recognition in TLE.

Epilepsy, Temporal Lobe↗

Genes and mutations in idiopathic epilepsy.

Partial or generalized idiopathic epilepsies, which account for up to 40% of all epilepsies, are characterized by a mostly benign course and no apparent etiology other than a genetic predisposition. So far, the genetic defects underlying three different idiopathic epilepsy syndromes have been identified: mutations in the CHRNA4- or CHRNB subunits of the neuronal nicotinic acetylcholine receptor are found in familial nocturnal frontal lobe epilepsy, while defects in the voltage-gated potassium channels KCNQ2 and KCNQ3 have recently been identified in benign familial neonatal convulsions. The syndrome of "generalized epilepsy with febrile seizures plus" can be caused by mutations affecting the voltage-gated sodium channel subunits SCN1B and SCN1A or the gamma 2-subunit of the GABA(A) receptor. The results of recent molecular studies contributed largely to our understanding of the etiology and pathophysiology of idiopathic epilepsies.

Epilepsies, Partial↗

Somatosensory evoked potentials in juvenile myoclonic epilepsy.

We analyzed the somatosensory evoked potentials (SEP) of 35 patients with juvenile myoclonic epilepsy (JME), 26 patients with idiopathic generalized epilepsy (IGE), and a control group consisting of 24 healthy people. The N19-P25 interval was significantly prolonged in the IGE group both as compared with the JME and control groups. This finding may be related to antiepileptic drug (AED) treatment, principally phenytoin (PHT). No differences were noted in N19 amplitude in any group. The P25 and N33 amplitudes were significantly higher in the JME group. In 5 patients of the JME group (14%) "giant SEP" were observed, but no differences were evident in the electroclinical characteristics with respect to the other JME patients. JME is one of the causes of giant-SEP.

Adolescent↗

A novel GABRG2 mutation associated with febrile seizures.

Mutations in the gene encoding the gamma2 subunit of the gamma-aminobutyric acid type A receptor (GABRG2) have been reported to cause childhood absence epilepsy (CAE), febrile seizures (FS), and generalized epilepsy with FS plus (GEFS+). The authors analyzed GABRG2 in 47 unrelated patients with CAE, FS, and GEFS+ and identified a novel mutation that cosegregated with FS. Electrophysiologic studies demonstrated altered current desensitization and reduced benzodiazepine enhancement in mutant receptors.

Belgium↗

Cortical hyperexcitability in progressive myoclonus epilepsy: a study with transcranial magnetic stimulation.

In progressive myoclonus epilepsy (PME), responses to afferent input are frequently abnormal. It is unclear whether the abnormality lies at the cortical, subcortical, or segmental level. To obtain evidence for an exaggerated effect on motor cortical excitability, we used peripheral nerve and transcranial magnetic stimulation in controls and subjects with idiopathic generalized epilepsy and PME. Mean threshold intensity was higher in those with idiopathic generalized epilepsy and PME than in controls, probably as a result of anticonvulsant treatment. A long-latency response to peripheral stimulation and an exaggerated facilitatory effect of peripheral stimulation on the motor evoked potential was present in subjects with PME. Latency differences between the late responses in the upper and lower limbs provided evidence against a segmental reflex and implicated rapidly conducting fibers in the spinal cord. Both the late response and the facilitatory effect had onset latencies consistent with a transcortical pathway, suggesting an exaggerated effect of afferent input on motor cortical excitability in PME.

Adaptation, Physiological↗

Primary and secondary bilateral synchrony in epilepsy: differentiation by estimation of interhemispheric small time differences during short spike-wave activity.

Estimation of interhemispheric small time differences (TDs) during spike-wave bursts in the EEG by coherence and phase analysis is useful for differentiation between primary bilateral synchrony (PBS) and secondary bilateral synchrony (SBS) in epilepsy. Because the previous method via Fast Fourier Transform needed long bursts for reliable analysis, a method using a 2-dimensional autoregressive model was newly developed to enable estimation of TDs even in 1.2 sec bursts, and applied to 19 epileptic patients with apparently bilaterally synchronous spike-wave bursts. At the onsets of bursts, estimated maximal TDs were 5.8 msec or less and inconsistent in leading hemispheres in 10 patients with a clinical diagnosis of idiopathic, cryptogenic or symptomatic generalized epilepsy indicating PBS, while the maximal TDs were 9.3-41.5 msec and consistent in leading in 7 patients with clinically symptomatic partial epilepsy and also in two with idiopathic and symptomatic generalized epilepsy suggesting SBS. Among 8 patients with bursts which suggested SBS and long enough for evaluation of intra-burst TD variation, TDs tended to disappear in the middle to end parts of the bursts in 5 cases, but not in the other 3, suggesting 2 different pathophysiological mechanisms in SBS.

Action Potentials↗

[Prognosis of epilepsy in psychoneurologically normal children].

Prognosis of 175 psychoneurologically normal children with the onset of epilepsy after 18 months of age were studied. The remission rate of partial epilepsy (81 of 107 cases, 76%) was higher than that of generalized epilepsy (34 of 56 cases, 61%). Prognoses for patients with sleep epilepsy (52 of 62 cases, 84%) were better than those for patients with waking epilepsy (63 of 101 cases, 62%). Most (95%) of the children with sleep epilepsy had partial epilepsy, including benign childhood epilepsy with centrotemporal spike (BECT, 36 cases) and partial epilepsy other than BECT (23 cases). Benign courses were not limited to BECT patients. Generalized waking epilepsy other than absence had the lowest remission rate. Eleven children exhibited mild mental retardation on last examination. Most of them had atypical absence and/or myoclonic seizures with the onset of seizure before 3 years of age. It appeared important to classify the epileptic children with regard to time of seizure occurrence as well as seizure type to determine their prognoses.

Adolescent↗

Carbamazepine versus valproate monotherapy for epilepsy.

BACKGROUND: Carbamazepine and valproate are drugs of first choice for epilepsy. Despite the lack of hard evidence from individual randomized controlled trials, there is strong clinical belief that valproate is the drug of choice for generalized epilepsies and carbamazepine for partial epilepsies. OBJECTIVES: To overview the best evidence comparing carbamazepine and valproate monotherapy SEARCH STRATEGY: Our search strategy included: (a) MEDLINE 1966-99, (b) The Cochrane Library 1999 issue 4, (c) The trial register of the Cochrane Epilepsy Group (d) the pharmaceutical industry. SELECTION CRITERIA: Randomized controlled trials comparing carbamazepine and valproate monotherapy for epilepsy. DATA COLLECTION AND ANALYSIS: This was an individual patient data review. Outcome measures were time to withdrawal of allocated treatment, time to 12 month remission, and time to first seizure post randomization. Data were analysed using the stratified Logrank test with results expressed as hazard ratios (HR) (95% CI), where HR>1 indicates an event is more likely on valproate. A test for an interaction between treatment and epilepsy type (partial versus generalized) was also undertaken. MAIN RESULTS: Results Data were available for 1265 patients from five trials, representing 85% of the patients recruited into the eight trials that met our inclusion criteria. The main overall results (HR 95% CI) were: Time to treatment withdrawal 0.97 (0.79-1.18), 12 month remission 0.87 (0.74-1.02), first seizure 1.09 (0.96-1.25) suggesting no overall difference for these outcomes. The test for an interaction between treatment and epilepsy type was non significant for time to treatment withdrawal and 12 month remission, but significant for time to first seizure. The age distribution of adults classified as having a generalized epilepsy indicate that significant numbers of patients may have had their epilepsy misclassified. REVIEWER'S CONCLUSIONS: We have found some evidence to support the policy of using carbamazepine as the first treatment of choice in partial epilepsies, but no evidence to support the choice of valproate in generalized epilepsies, but confidence intervals are too wide to confirm equivalence. Misclassification of patients may have confounded our results, and has important implications for the design and conduct of future trials.

Adult↗

Potentiation and modification of recruiting responses precedes the appearance of spike and wave discharges in feline generalized penicillin epilepsy.

Recruiting responses (RR) were evoked by stimulation of nucleus centralis medialis in awake and painlessly immobilized cats. Following the administration of sodium penicillin G (350,000 IU/kg i.m.) and at a time preceding the development of generalized spike-and-wave discharge we observed a strong potentiation of RR in 10 out of 15 experiments (50-200% increase in amplitude). The major feature of wave form modification consisted mainly of a development or increase of positive phases of individual recruiting waves. In between such large amplitude negative-positive recruiting waves a slow negative wave developed. One of every two recruiting waves was often diminished when the preceding recruiting wave had reached considerable amplitude. The changes in the RR were antagonized by barbiturates and by caffeine. In conjunction with previous evidence these results support the hypothesis that spikes of spike-and-wave discharges in FGPE are generated by similar thalamocortical volleys as those creating RR and spindles. They further suggest that the crucial neuronal mechanism underlying this effect of penicillin is a shift in the emphasis from distal apical dendritic thalamocortical synapses on cortical pyramidal neurons to more proximal ones.

Action Potentials↗

Sleep spindles in epilepsy.

Spindles are a ubiquitous phenomenon in sleep, but their physiology and the effects of neurologic disorder on their frequency and amplitude are incompletely understood. We compared the incidence of three commonly defined spindle types (14-15 Hz, 12-13 Hz, and 10 Hz) and the frequency and amplitude of spindles during Stage II sleep in 50 patients with complex partial, partial and secondarily generalized, and primary generalized seizures, with and without interictal behavioral symptoms. All patients had 12-13 Hz and 14-15 Hz spindles of symmetric character in C3-A1 and C4-A2 derivations during prolonged sleep-deprived EEG recordings, which were normal except for partial or generalized epileptiform activity. Seventy-one per cent of complex partial seizure patients had 10 Hz spindles, and they occurred in 50% of the other two groups, predominating among those with interictal behavioral symptoms in all groups. Spindle frequency was significantly less in patients with generalized epilepsy than with partial seizures, and patients with complex partial seizures and partial seizures with secondary generalization differed significantly in spindle frequency. Spindle frequency was significantly lower with polypharmacy than with monotherapy. Patients whose regimens included phenobarbital had significantly lower spindle frequencies and spindle frequencies differed significantly between phenytoin and carbamazepine. Differences in spindle frequency may be due to residual medication effects, underlying encephalopathy or physiological differences between partial and generalized epilepsy.

Adolescent↗

Genetic localization of the familial adult myoclonic epilepsy (FAME) gene to chromosome 8q24.

OBJECTIVE: To identify the genetic locus for the familial adult myoclonic epilepsy (FAME) gene. BACKGROUND: Idiopathic generalized epilepsy (IGE) represents a collection of disorders in which affected individuals present with recurring seizures that have diffuse onset on EEG. These individuals have no known structural cerebral lesions or other identifiable etiology. IGE accounts for approximately 40% of all epilepsies. FAME is a type of IGE characterized by autosomal dominant inheritance, adult onset, varying degrees of myoclonus in the limbs, rare tonic-clonic seizures, and a benign course. METHODS: We investigated four previously reported Japanese kindreds and performed a genome-wide screen with genetic linkage analysis. RESULTS: Clinical characterization and sampling of 30 individuals in four families revealed that 21 had the FAME phenotype. We defined a 4.6-cM region on chromosome 8q24 (maximum lod score of 4.86 at theta = 0) that contains the FAME gene. CONCLUSIONS: The identification and characterization of the FAME gene allows us to better understand the molecular basis of FAME. Such knowledge may provide clues to understanding the molecular basis of the clinically similar, and more common, juvenile myoclonic epilepsies, and other generalized seizure disorders that have thus far eluded genetic approaches.

Adult↗

Long-term effectiveness of antiepileptic drug treatment and seizure recurrence in patients with epilepsy.

We studied the rate of seizure recurrence in 334 patients with epilepsy who had received antiepileptic drug (AED) therapy for at least eight years. During the three-year "observation period" (April 1985-March 1988), 163 or 48.8% of the 334 patients were considered to be seizure-free. Seizures were absent in 53 or 81.5% of 65 patients with idiopathic generalized epilepsy, 48 or 40% of 120 with temporal lobe epilepsy, 39 or 39.4% of 99 with partial epilepsy other than those involving the temporal lobe, 2 or 8.3% of 24 with symptomatic generalized epilepsy and 21 or 80.8% of 26 with other epilepsies. Of the 163 patients, 15 or 9.2% suffered seizure(s) during the three-year "follow-up period" (April 1988-March 1991). There was no difference among the different types of epilepsy with respect to seizure recurrence rates. Compared with the 15 patients whose seizures recurred, more of the 148 patients with nonrecurring seizures received AED monotherapy (p < 0.05). However, no significant differences were seen between the two groups for other background factors.

Adult↗

Pattern-reversal VEP and cortical SEP latency prolongations in epilepsy.

Twenty ambulatory outpatients with generalized tonic-clonic seizures with primary generalized discharges and photoconvulsive response on electroencephalogram (EEG) and 11 ambulatory outpatients with partial complex seizures with or without secondary generalization were studied with pattern-reversal light-emitting diode (LED) stimulator visual evoked potential (VEPs) and short-latency median nerve cortical somatosensory evoked potentials (SEPs). The patients with primary generalized epilepsy had significantly prolonged latencies of VEP components P2 and N3 and SEP component P22. The patients with partial epilepsy had significantly prolonged latency of VEP component N3. It is concluded that both functional and structural factors may cause a slowing of central impulse conduction.

Adolescent↗

Effect of sodium valproate on psychomotor performance in children as a function of dose, fluctuations in concentration, and diagnosis.

Forty-six children receiving sodium valproate monotherapy, and with well-controlled seizures, were tested three times, at weekly intervals in the morning, on an extensive battery of psychomotor tests. The first session was a practice session to minimize subsequent practice effects. On one of the remaining 2 test days, morning medication was delayed until after testing (low concentration condition), whereas sodium valproate was given before testing on the alternate session (high concentration day). The data were analyzed for the effects of diagnosis (partial vs. generalized epilepsy), dose (above or below 20 mg/kg/day), and time of medication (low and high drug concentration days). Four variables discriminated between the diagnostic groups, all favoring children with generalized epilepsy. Another four measures were significantly associated with dose, with those on lower doses performing at a superior level. Time of medication had virtually no effect on performance, however. The findings were related to previous diagnostic and dosage research. Although a deterioration in performance at higher doses appears to be consistent with other dosage research, the absence of an effect due to time of medication suggests that performance does not fluctuate between drug administrations.

Adolescent↗