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PubMed2001

The perception of memory failures in patients with epilepsy.

The aim of the study is to evaluate the correlation between subjective memory complaints and neuropsychological tests in the epilepsy population. We administered a Self Report Memory Questionnaire, based on possible everyday memory failures, two questionnaires on anxiety and depression and a battery of cognitive tests to 150 patients with epilepsy (n=100 with partial epilepsy, n=50 with idiopathic generalized epilepsy) and a control group (n=50). A discrepancy between the results of the memory questionnaire and the cognitive tests was found in the epilepsy patients: the Self Report Memory Questionnaire did not show any correlation with the psychological tests. The same discrepancy was not seen in the controls, where the memory questionnaire was related to two verbal memory tests. Furthermore, patients with epilepsy reported greater difficulties on the Self Report Memory Questionnaire than the controls (P < 0.05). It appeared that the tendency to overstate memory problems was mainly related to anxiety and depression, but was not connected with the type of epilepsy, nor with its duration (in years). Seizure frequency, on the other hand, seemed to greatly influence mood, which in turn is probably affect subjective memory perception.

Adult↗

PubMed1999

Psychosocial and economic problems of parents of children with epilepsy.

The parents of children with epilepsy (PCE) face multiple psychosocial and economic problems that are often neglected. We undertook this study to ascertain these problems among the patients attending a tertiary referral center for epilepsy in India. A structured questionnaire was administrated to parents of 50 children aged between 5-10 years and having epilepsy for more than 1 year's duration. Some 52% of the children had partial epilepsy whilst the remaining had generalized epilepsy. The median seizure frequency was one per 6 months. The majority of the patients (86%) were living in villages. The family income was less than 1000 Rs per month (1 USD = 42 INR) for 66% of the patients. A decline in social activities, after the onset of epilepsy in their children, was reported by 80% of the parents. Daily routines were significantly affected in over 75% of the parents. Parents had been experiencing frustration (52%) and hopelessness (76%), whilst 60% were in financial difficulties. The most important item of expenditure was cost of drugs or cost of travel to hospital for 54% and 36% parents respectively. Impaired emotional status and poor social adaptation were co-related with the severity of epilepsy (frequent seizures/generalized seizures/attention disorder) and low economic status of the parents. These observations need to be borne in mind while organizing rehabilitation programs for epilepsy.

Child↗

PubMed2004

Genome-wide linkage scan of epilepsy-related photoparoxysmal electroencephalographic response: evidence for linkage on chromosomes 7q32 and 16p13.

Photoparoxysmal response (PPR) is an abnormal visual sensitivity of the brain in reaction to intermittent photic stimulation. It is an epilepsy-related electroencephalographic trait with high prevalence in idiopathic epilepsies, especially in common idiopathic generalized epilepsies (IGEs), such as childhood absence epilepsy and juvenile myoclonic epilepsy. This degree of co-morbidity suggests that PPR may be involved in the predisposition to IGE. The identification of genes for PPR would, therefore, aid the dissection of the genetic basis of IGE. Sixteen PPR-multiplex families were collected to conduct a genome-wide linkage scan using broad (all PPR types) and narrow (exclusion of PPR types I and II and the occipital epilepsy cases) models of affectedness for PPR. We found an empirical genome-wide significance for parametric (HLOD) and non-parametric (NPL) linkage (Pgw(HLOD)=0.004 and Pgw(NPL)=0.01) for two respective chromosomal regions, 7q32 at D7S1804 (HLOD=3.47 with alpha=1, P(NPL)=3.39x10(-5)) and 16p13 at D16S3395 (HLOD=2.44 with alpha=1, P(NPL)=7.91x10(-5)). These two genomic regions contain genes that are important for the neuromodulation of cortical dynamics and may represent good targets for candidate-gene studies. Our study identified two susceptibility loci for PPR, which may be related to the underlying myoclonic epilepsy phenotype present in the families studied.

Chromosome Mapping↗

PubMed2006

Genetic dissection of the common epilepsies.

PURPOSE OF REVIEW: Only two functionally validated susceptibility genes, CACNA1H and GABRD, have so far been identified in the common epilepsies using a candidate gene approach. The difficulty with the alternative statistical approach, where none of the suggested candidates has been functionally validated, may partly be due to the posited genetic architecture of the common epilepsies, such as the idiopathic generalized epilepsies. A subset of both rare and common variants from a much larger pool of susceptibility genes may contribute to disease risk. We review methods and designs for the genetic dissection of common epilepsies. RECENT FINDINGS: Genetic association studies, though theoretically more powerful than linkage analysis, have not yet delivered validated susceptibility genes. Methodological flaws can undermine such studies but are correctable. Concerns remain, however, about the extent of underlying genetic heterogeneity in common epilepsies. Genome-wide association studies are increasingly feasible, but issues remain about their conduct and analysis. Meta-analysis may resolve conflicting association studies, facilitated by the establishment of databases of genetic association studies. Newer multi-locus and admixture mapping approaches are attractive alternatives to traditional association studies and may offer new insights into identifying epilepsy genes. SUMMARY: We conclude by emphasizing the importance of deeper endophenotyping using electroclinical, imaging, and molecular approaches to dissect the common epilepsies.

Chromosome Mapping↗

PubMed2006

Retinal nerve fiber layer and macular thickness in adolescents with epilepsy treated with valproate and carbamazepine.

PURPOSE: To evaluate retinal nerve retinal nerve fiber layer (RNFL) and macular thickness by using optical coherence tomography (OCT) in epileptic adolescents before and during monotherapy with valproic acid (VPA) and carbamazepine (CBZ). METHODS: We examined prospectively 45 epilepsy patients with partial and generalized epilepsy. The patients were evaluated before the beginning of therapy and after 1 year of VPA or CBZ monotherapy. Forty-five untreated healthy controls were evaluated at baseline and after 1 year. RESULTS: At the beginning of the study, the two groups of patients showed RNFL and macular thickness measurements similar to control values. At the end of the follow-up, the data of the three groups were similar to baseline, showing no significant differences in the evaluated parameters. CONCLUSIONS: The present study demonstrates that no modification of RNFL and macular thickness parameters is found after 1 year of treatment with VPA and CBZ monotherapy.

Adolescent↗

PubMed1990

Event-related potential (P300) in epilepsy.

The P300 component of auditory event-related potential was studied in 39 patients with temporal lobe epilepsy (TLE), 26 with idiopathic generalized epilepsy (IGE) and 28 controls. The age-corrected P300 latencies were significantly longer in TLE patients compared with those in IGE patients and controls. Neither the duration of epilepsy nor clinical manifestation was related to the P300 component in the same epileptic syndrome. The age-corrected P300 latencies recorded from Cz were significantly prolonged in TLE patients with bilateral temporal EEG foci compared with those with unilateral focus. The effects of anti-epileptic drugs on the P300 component were not significant. Our findings imply that prolonged P300 latency in TLE patients, especially in those with bilateral EEG foci is due to damage of the hippocampus, which is potentially an epileptogenic focus.

Acoustic Stimulation↗

PubMed1992

Interictal brain 99Tc-HM-PAO SPECT hypoperfusion in patients with unstable partial epilepsy and normal CT.

Brain perfusion was studied interictally with 99mTc-HM-PAO SPECT in 47 adult patients with partial epilepsy and normal brain CT. Epilepsy was classified as secondarily generalized in 24 patients, as complex partial in 17 patients and as simple partial in 6 patients. In 24 patients good seizure control was not achieved as these patients had a median number of 78 seizures during the preceding month, while in the rest of the patients seizure control was relatively good (less than 6 seizures during preceding month). Local brain hypoperfusion was observed in 41 or 87% of the patients. Hypoperfusion was located close to the EEG foci in 76% and equally often with temporal and frontal foci. Hypoperfusion and the EEG focus were located on the same side in 83%. Hypoperfusion was more frequent in secondarily generalized epilepsy and simple partial epilepsy than in complex partial epilepsy. Left-sided hypoperfusion was especially associated with complex partial epilepsy. It is likely that the significant epileptogenic brain area was revealed in patients with SPECT focus and EEG focus in the same brain area. In one of our patients MRI showed a small temporal lesion which on successful removal was identified as a low-grade oligodendroglioma. Abnormalities of regional brain uptake of HM-PAO demonstrated by SPECT in patients with partial epilepsy and normal brain CT give further information about pathophysiology in partial epilepsy; this may be of use both for selecting appropriate therapy and in presurgical localization of foci.

Adult↗

PubMed1985

The benign infantile epilepsies with evoked spikes.

The International Classification of the Epilepsies defines two types of generalized epilepsies: primary (mainly functional) and secondary (organic) and only one type of partial epilepsy, (organic). Recent studies show the existence of a group of "functional" or "mostly functional" partial epilepsies. Among these, a particular place is occupied by the benign infantile epilepsies "with evoked spikes," described during the last 10 years. These are forms with a very particular development, characterized in all cases by 4 typical phases; the last one is the clinical phase with epileptic seizures. The prognosis is very good. The discussion concerns the similarities and the differences between these epilepsies versus the other partial benign epilepsies.

Child↗

PubMed2003

Sodium channel alpha1-subunit mutations in severe myoclonic epilepsy of infancy and infantile spasms.

BACKGROUND: Mutations in SCN1A, the gene encoding the alpha1 subunit of the sodium channel, have been found in severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). Mutations in SMEI include missense, nonsense, and frameshift mutations more commonly arising de novo in affected patients. This finding is difficult to reconcile with the family history of GEFS+ in a significant proportion of patients with SMEI. Infantile spasms (IS), or West syndrome, is a severe epileptic encephalopathy that is usually symptomatic. In some cases, no etiology is found and there is a family history of epilepsy. METHOD: The authors screened SCN1A in 24 patients with SMEI and 23 with IS. RESULTS: Mutations were found in 8 of 24 (33%) SMEI patients, a frequency much lower than initial reports from Europe and Japan. One mutation near the carboxy terminus was identified in an IS patient. A family history of seizures was found in 17 of 24 patients with SMEI. CONCLUSIONS: The rate of SCN1A mutations in this cohort of SMEI patients suggests that other factors may be important in SMEI. Less severe mutations associated with GEFS+ could interact with other loci to cause SMEI in cases with a family history of GEFS+. This study extends the phenotypic heterogeneity of mutations in SCN1A to include IS.

Amino Acid Sequence↗

PubMed2000

[Reflex epilepsies].

INTRODUCTION: Reflex seizures are provoked by a specific sensory stimulus. Approximately 6% of all epileptic patients have reflex seizures. For identification of these seizures it is necessary to take a directed history and make an EEG study whilst the patient is being exposed to the stimulus, which will confirm the diagnosis. DEVELOPMENT: Many stimuli are effective in provoking reflex seizures, the commonest are visual. Amongst the various epileptic syndromes there are different types of epilepsies with reflex seizures which generally correspond to idiopathic generalized epilepsies. The physiopathogenic mechanisms are usually complex. The cerebral cortex corresponding to the function which induces the epileptic crisis is hyperexcitable, and is the cause of an identifiable lesion or dysfunction without an underlying lesion. CONCLUSION: The diagnostic importance of reflex seizures is that when some formerly drug-resistant patients can control the mechanism which triggers off their seizures they attain good control of them.

Brain↗

PubMed1999

Epilepsy and paroxysmal movement disorders in families: evidence for shared mechanisms.

The epilepsies have been regarded as clinically distinct from the paroxysmal movement disorders. Recently, a variety of ion channel defects have been identified as the biological basis of certain familial epilepsies and paroxysmal movement disorders. We studied two families with the co-occurrence of epilepsy, movement disorders and migraine. Information was obtained on 147 individuals in the two families. In family WF, there was a co-occurrence of epilepsy (benign infantile convulsions, idiopathic generalized epilepsy), episodic ataxia (with cerebellar atrophy and without myokymia) and common migraine. In family CL, epilepsy (febrile seizures, febrile seizures plus), kinesigenic paroxysmal dyskinesia and migraine (including hemiplegic migraine) were observed in various combinations over 3 generations. The observations in these two families, together with review of the literature, suggest that the co-occurrence of epilepsy (particularly benign infantile convulsions), paroxysmal movement disorders and migraine is not due to chance. Thus, these distinct clinical phenomena could have a shared biological basis and ion channel defects are an attractive possibility.

Adolescent↗

PubMed2001

[Epilepsy in patients with severe motor and intellectual disabilities: a long-term follow-up].

Long-term prognosis of epilepsy was investigated on 117 institutionalized patients with severe motor and intellectual disabilities, who were above 15 years of age in 1977, for a 20-year-period from 1977 to 1997. The incidence of epilepsy was 64.1% (75 patients), which was active in 28 patients (37.3%). The patients with the most severe psychomotor disabilities (bedridden and DQ < 20) showed the highest incidence of epilepsy (85.0%). Patients who died during the follow-up period showed higher incidence of active epilepsy (p < 0.01). During the follow-up of 94 surviving patients, persistence, relapse, and onset of seizures were frequent in patients with most severe intellectual disability, whereas those with less severe intellectual disability (20 < DQ < 35) were all seizure-free. Twenty-one patients had active epilepsy; symptomatic partial epilepsy in 17 (81.0%) and generalized epilepsy in 4 (19.0%). Notably, 5 of the 6 patients with persistent frequent seizures had age-dependent epileptic encephalopathy; persistent Lennox-Gastaut syndrome (LGS) (2 patients), severe epilepsy with multiple independent spike foci evolved from West syndrome (WS) and LGS (2 patients), and partial epilepsy with the history of LGS (1 patient).

Adolescent↗

PubMed2001

[New antiepileptic drugs in childhood epilepsies: indications and limits].

Regarding the antiepileptic drugs (AEDs) in children, it was recently shown that they have a specific profile of efficacy and also of worsening according to the different epilepsy syndromes. However, the therapeutic profile of the most recent compounds is still not completely established in children because of the high number of syndromes and the difficulty to perform controlled studies in this age range. Controlled studies are most often first performed in adults and they begin in children whereas the new drug is already approved. However, some new AEDs dramatically improved seizure control, particularly in some severe epilepsy syndromes such as West syndrome and Lennox-Gastaut syndrome. Vigabatrin demonstrated a remarkable efficiency in infantile spasms whereas it tends to worsen myoclonic epilepsies, absence epilepsy and idiopathic partial epilepsy. Lamotrigine is efficient in absence epilepsy and symptomatic or cryptogenic generalized epilepsies such as Lennox-Gastaut syndrome and myoclonic astatic epilepsy. By contrast, lamotrigine increases the frequency of seizures in severe myoclonic epilepsy in infancy (Dravet syndrome) as well as in some cases of idiopathic partial epilepsy. Felbamate remains indicated as third line drug in refractory Lennox-Gastaut syndrome provided blood parameters are controlled. The therapeutic profile of oxcarbazepine is closed to that of carbamazepine. The efficacy of topiramate was demonstrated in partial epilepsy, but the other indications remain to be précised. Pediatric studies using gabapentin and tiagabine disclosed encouraging results in partial epilepsy. Clinical trials with stiripentol represent an example of strategy for developing a new AED in children; it recently demonstrated, in association with clobazaru, efficacy in a severe myoclonique epilepsy in infancy.

Anticonvulsants↗

PubMed2002

[Childhood epilepsy in Okayama Prefecture, Japan--a neuroepidemiological study].

Epidemiological surveys on epilepsy have been carried out repeatedly in Japan. However, at present, a population-based survey according to the International Classification for Epileptic Syndromes is considered to be especially important. We therefore carried out a population-based survey on children with epilepsy under thirteen years of age, who resided in Okayama Prefecture on December 31, 1999 as the prevalence day. The population of children in Okayama Prefecture under thirteen years of age on the prevalence day was 250,997. The lists of children with epilepsy were collected from the medical records of 45 hospitals, 36 clinics and 3 institutions in and around Okayama Prefecture. 1) 2,222 cases with active epilepsy were identified. The prevalence rate was 8.9 per 1,000. 2) This prevalence rate was almost equal to the previous result (8.2 per 1,000) given by another survey undertaken in 1975 for children under ten years of age in Okayama Prefecture. 3) If the cases with single seizure and/or the cases with seizures induced by fever are excluded, the prevalence rate decreased to 5.5 per 1,000. 4) 2,026 (91.2%) of the 2,222 cases were classified into three major categories of the International Classification of Epileptic Syndromes. They consisted of 1,557 cases (76.8%) with localization-related epilepsy, 449 cases (22.2%) with generalized epilepsy and 20 cases (1.0%) with undetermined epilepsy. 5) 303 (15.0%) of the 2,026 cases were classified into the epileptic syndromes. However, the majority of other cases consisted of nonspecific types of epilepsy, and could not be classified in detail. 6) The guideline for informed consent in epidemiological study published in 2000 by the Committee of the Japanese Ministry of Public Welfare will be useful for neuroepidemiological studies in the future.

Age Factors↗

PubMedDate not supplied

[Lipid peroxidation in adult epileptic patients treated with valproic acid].

INTRODUCTION: Free radicals play an important role as regulatory mediators in cellular signalling processes; however, when overproduced or when antioxidant defence systems are weakened, they are cause of cellular damage. Excessive amount of free radical production has been related with a variety conditions, like aging, different kind of diseases, and xenobiotics biotransformation; this last process includes the metabolism of lipid soluble drugs. An increase in oxidative stress has been described in series of treated epileptic patients. OBJECTIVE: To evaluate the susceptibility to plasma lipid peroxidation in samples from epileptic patients treated with valproic acid monotherapy, studying if the formation of lipid peroxides was related with plasma drug concentration, patients' sex or the kind of epilepsy suffered. PATIENTS AND METHODS: Peroxidated lipids (LPO) were measured by spectrofluorometry before and after induction of an oxidative Fenton reaction in 76 epileptic patients and 4 healthy subjects. RESULTS: After induction of the Fenton reaction, but not in basal conditions, lipid peroxidation showed a lineal relationship with valproate plasma levels. Oxidized LPO values were also significantly higher in samples from patients with partial epilepsies than in those with generalized epilepsies. Likewise, a significant gender effect was observed, being values from epileptic women noticeably higher than those of epileptic men. CONCLUSIONS: Plasma from epileptic patients receiving valproic acid evidences an increased vulnerability to lipid peroxidation which seems to be related with drug amount in the body, subject's sex, and epilepsy type.

Adolescent↗

PubMed1988

[Neurophysiological and therapeutic evaluation of stiripentol in epilepsy. Preliminary results].

The main objective of this study was to determine whether stripentol (STP) alleviates side-effects commonly observed in treated epileptic patients, since preliminary data suggested a positive psychotropic effect. A secondary objective was an evaluation of drug efficacy. Eleven patients with either a drug-resistant epilepsy or toxic effects of AEDs completed the study. Ten had symptomatic partial epilepsies and one an idiopathic generalized epilepsy. STP was added to the baseline therapy (1 or 2 AEDs) and the dose of the baseline AEDs was reduced to maintain plasma levels unchanged (mean reduction: PB 26%, PHT: 49%, CBZ: 38%). Several motor, perceptual and attention tasks and the Washington Psychosocial Seizure Inventory were performed before and after STP administration. Seizure frequency and clinical side-effects were evaluated during a baseline period and after two months of constant therapy. Effects of repeated administration of the neuropsychological battery were assessed by administration of the battery on two occasions at 12-week interval to a randomized subgroup of patients. No practice effect was observed. A trend of improvement (p less than 0.05) in the performance of two tasks requiring sustained attention was noted. Previous side-effects (mainly drowsiness) decreased or disappeared in 7 of 9 patients who became more alert. Six of the nine uncontrolled patients experienced a decrease in seizure frequency equal to or larger than 50 per cent.

Adult↗

PubMed1996

[A phase 3 clinical trial of 123I-iomazenil, a new central-type benzodiazepine receptor imaging agent (Part 3)--Report on clinical usefulness in epilepsy].

A Phase 3 clinical trial of 123I-Iomazenil (IMZ), a tracer which binds specifically to central-type benzodiazepine receptors (BZR), was performed, and the clinical usefulness of IMZ was evaluated in 121 patients with epilepsy (106 cases with partial epilepsy and 15 cases with generalized epilepsy). A regional abnormality in the BZR distribution was detected in late IMZ images in 20 of 24 cases without abnormal MRI and/or X-ray CT findings. Moreover, only 16 of these 20 cases showed abnormal findings in the cerebral blood flow (CBF) images. In partial epilepsy, abnormal regions in late IMZ images agreed or partially agreed with epileptic foci estimated from the clinical symptoms of epileptic seizures, interictal EEG, and MRI and/or X-ray CT findings in 76%, 70% and 96% of the cases detected. These regions also agreed or partially agreed with the estimated epileptic foci in 92% of the cases with foci estimated by combination of those three methods and in 72% of those estimated by ictal EEG. The agreement or partial agreement rates of late IMZ images with each of the other methods were higher than those of CBF images, although the differences were not significant. For surgically-proven epileptic foci without any abnormality in the CBF image, abnormal regions were detected in late IMZ images. These findings suggest that IMZ SPECT is a useful new tool for detecting epileptic foci based on the distribution of BZR in the brain.

Adult↗

PubMed1997

[Epilepsy in childhood].

With a morbidity of 0.8%, epilepsy in childhood is one of the most frequent chronic diseases of the CNS. Improved diagnostic and therapeutical options of the last two decades made it possible that today 60-70% of the patients are without attacks for a long period and are fully socially integrated. Epilepsy is clinically classified into generalized epilepsies; which are of symptomatic origin in 50% of the cases, and focal epilepsies, which are even more frequent caused by CNS-injuries. The diagnosis of epilepsy results from the synopsis of the clinical picture of the attack and the electro-encephalogram (EEG), in case of doubts from the analysis of the video-EEG. The anti-convulsive drug therapy is undertaken as long-term treatment when free of attacks for 3-5 years and has to be monitored clinically as well as biochemically. The option of epilepsy-surgical procedures in a center of epilepsy should be considered in cases of a resistance to drug therapy. The tight cooperation with the family physician is of great importance for the ambulant epileptic care, others like social service, careers guidance and psychologic service have to be integrated.

Anticonvulsants↗