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[Etiological diagnosis of epilepsy: value of computerized axial tomography (C.A.T.) (author's transl)].

The authors appraise the value of CAT in the study of epilepsy from their personal experience and from the few published works that are available. The CAT confirms and supports a large number of already acquired facts:--the almost complete absence of cerebral lesions in "functional" epilepsies (primary generalized epilepsies and benign childhood epilepsy with rolandic paroxysms);--the large number of abnormalities in the secondary generalized epilepsies (West syndrome, Lennox-Gastaut syndrome) where the majority of patients present a bilateral fronto-temporal atrophy;--the high percentage of cerebral lesions in partial epilepsies. In this case, the CAT is especially notable in revealing etiologies in 63 p. 100 of cases. They include: tumors, abcesses, empyemas, angiomas, cerebral infarctions, cerebral atrophies, post-traumatic lesions, etc... From this study, it can be concluded that positive diagnosis of epilepsy is still made on the basis of clinical and electroencephalographic data, with the CAT used to facilitate the etiological diagnosis.

Adolescent↗
PubMed1975

A controlled trial on clonazepam INN (Ro 5-4023, Rivotril (R)) in the treatment of focal epilepsy and secondary generalized grand mal epilepsy.

In a controlled clinical investigation based on 14 patients with focal seizures and 3 patients with secondary generalized grand mal epilepsy, all with insufficient response to conventional anti-epileptic treatment, clonazepam (Rivotril(R)) combined with previous anti-epileotic drugs was compared with placebo combined with the same drugs. The trial was singleblind cross-over with sequential analyses. With a daily dose, depending upon age, of usually 3-6 mg, the antiepileptic effect of Clonazepam was significantly superior to placebo and was estimated as remarkably good. Side-effects in the form of somnolence, fatique, drowsiness and co-ordination disturbances occurred in most of the patients but subsided spontaneously or could be managed by slow increase or slight reduction in dosage.

Adolescent↗
PubMed2000

Antiphospholipid and antinuclear antibodies in patients with epilepsy or new-onset seizure disorders.

PURPOSE: The increased prevalence of autoantibodies in patients with epilepsy has been traditionally regarded to be a consequence of antiepileptic drugs. The purpose of this study was to measure autoantibodies in well-defined groups of patients with seizures to determine the effects of epilepsy and antiepileptic medications on the presence of autoantibodies. PATIENTS AND METHODS: We studied the frequency of antinuclear antibodies, anti-beta2-glycoprotein I antibodies, and anticardiolipin antibodies in 50 patients with therapy-resistant localization-related epilepsy, 50 patients with generalized epilepsy syndromes, 52 patients with a newly diagnosed seizure disorder but no antiepileptic medication, and 83 healthy controls. RESULTS: Compared with controls, newly diagnosed patients had a significantly greater prevalence of immunoglobulin (Ig) G class anticardiolipin antibodies (21% versus 7%); the prevalence was 14% in patients with localization-related epilepsy and 8% in patients with generalized epilepsy. The prevalence of IgM class anticardiolipin antibodies was significantly greater in all seizure groups (60% in localization-related epilepsy, 42% in generalized epilepsies, and 33% in newly diagnosed patients) compared with controls (7%). Antinuclear antibodies were significantly more common in newly diagnosed patients (21%) and localization-related epilepsy (24%) compared with controls (12%). When patients with generalized epilepsy (8%) were used as the reference group, antinuclear antibodies were also significantly more frequent in localization-related epilepsy (relative risk [RR] = 2.9, 95% confidence interval [CI]: 1.1 to 8.2) and newly diagnosed seizures (RR = 3.4, 95% CI: 1.2 to 9.3). There were no consistent associations between autoantibodies and specific antiepileptic medications. CONCLUSIONS: The prevalence of autoantibodies is greater in patients with epilepsy, including newly diagnosed seizure disorder. The increased prevalence of autoantibodies is more strongly associated with epilepsy than with antiepileptic drugs, perhaps indicating that immune dysregulation may be commonly associated with epilepsy.

Adult↗
PubMed1995

[Generalized idiopathic epilepsy with refractory absence seizures in the adult].

The prognosis for generalized epilepsy with absence seizures starting in childhood and adolescence (GEA) must be given cautiously because of the possibility that seizures may persist into adulthood and occur along with tonic-clonic seizures. Such an unfavorable course may be due to factors that are intrinsic to the various epileptic syndromes involving absences and/or to individual patient characteristics. An additional factor of particular importance in GEA is inadequate treatment. We describe 15 adult patients with GEA whose mean age when examined was 41.3 years. All had experienced absence seizures since childhood and 12 had had convulsive seizures. Most were following haphazardly combined therapies. An average of 4 years was needed to modify treatment and achieve remission of seizures in 11 of the 13 cases followed for more than 1 year. We emphasize the efficacy of valproate (in 14 of 15 patients) and its combination with ethosuximide (4 patients). GEA should not be considered refractory until appropriate use of these drugs has been tried; rather it is a syndrome that may go into remission even after decades of persistent seizures.

Adult↗
PubMed2005

Educational underachievement in children with epilepsy: a model to predict the effects of epilepsy on educational achievement.

In this study, we evaluated the impact on educational achievement of four characteristics of epilepsy individually and combined: epilepsy syndrome (type of epilepsy), seizure type, the frequency of epileptiform electroencephalographic (EEG) discharges, and the effect of antiepileptic treatment. Simultaneously, the effect on cognitive function and the relationship between educational underachievement and cognitive impairment were evaluated, focusing on memory, attention, speed of information processing, and intelligence level. This study was an open, controlled, parallel-group, nonrandomized clinical investigation. Eligible patients were selected when referred to our center for assessment of relationships between epilepsy and learning impairment in the years 1997 to 2001. Separately, children without neurologic deficit and without educational delay were assessed with the same tests as the children with epilepsy. This latter group is used in this study as a control group. One hundred seventy-six children with epilepsy and 113 controls were included. Gender distribution and age were comparable for the two groups. All children were in regular primary education. The children were assessed with a test battery consisting of tests for educational achievement, cognitive tests and tests for reaction time, and tests for memory and intelligence. Multivariate analysis of variance for tests of educational achievement showed a statistically significant effect for type of epilepsy (F = 4.386; P = .04), caused by the statistically lower scores for patients with localized epilepsy and symptomatic generalized epilepsy. For the reaction-time tests, a statistically significant effect for epileptiform EEG discharges (F = 3.165; P = .01) and treatment (F = 4.472; P = .001) on both vigilance tests was found, caused by patients with frequent epileptiform EEG discharges and polytherapy. Two-way interactions showed an interaction with type of epilepsy, with more patients with symptomatic generalized epilepsy having frequent epileptiform EEG discharges and polytherapy. For memory, none of the analyses showed statistically significant effects. For intelligence only for type of epilepsy, a statistically significant effect was found (F = 10.174; P = < .001). We propose a model with the type of epilepsy (epilepsy syndrome) as the dominant factor explaining educational underachievement in children with epilepsy. Such educational underachievement is most prominent for the localized and symptomatic generalized epilepsies, which suggests a dominant impact of underlying etiology (brain dysfunction or damage). These epilepsies are characterized specifically by a lower intelligence; hence, this could be the primary cognitive factor mediating between the type of epilepsy and educational underachievement. From the other factors, treatment (the use of polytherapy) and frequent epileptiform EEG discharges are associated with impaired vigilance, which could have an additional influence on educational achievement. These factors are, however, not independent of the type of epilepsy.

Anticonvulsants↗
PubMed2005

Efficacy and safety of topiramate in refractory epilepsy of childhood: long-term follow-up study.

This study aimed to evaluate the long-term efficacy and safety of topiramate in treating children with drug-resistant epilepsy. A multicentric, retrospective, open-label, add-on study was undertaken of 277 children (mean age 8.4 years; range 12 months to 16 years) affected by drug-resistant epilepsy. The efficacy was rated according to the seizure types and epilepsy syndrome. After a mean period of 27.5 months of treatment (range 24-61 months), 11 patients (4%) were seizure free and 56 (20%) had more than 50% reduction in seizure frequency. The efficacy of topiramate treatment was noted in localization-related epilepsy and in generalized epilepsy. In addition, in a group of 114 patients, we compared the initial efficacy (evaluated after a mean of 9 months of follow-up) and the retention at a mean of 30 months of topiramate with regard to loss of efficacy (defined as the return to the baseline seizure frequency). Fifty-five (48%) of 114 patients were initial responders. The retention at a mean of 30 months was 23 of 114 patients (20%), 4 of whom (3.5%) were still seizure free. A loss of efficacy occurred in 32 of the 55 initial responders (58%). It was prominent in patients with generalized epilepsy, such as symptomatic infantile spasms and Lennox-Gastaut syndrome, as well as in those with Dravet syndrome. By contrast, a well-sustained topiramate efficacy was noted among patients with localization-related epilepsy. Globally, adverse events were observed in 161 patients (58%) and were mainly represented by weight loss, hyperthermia, sedation, and nervousness, which, in most cases, disappeared after slowing titration or reducing the dosage of the drug. In conclusion, the present long-term study confirms that topiramate represents a useful drug effective in a wide range of seizures and epilepsy syndromes. Moreover, preliminary data seem to suggest that the efficacy of topiramate, when evaluated in the long-term perspective, is more sustained in localization-related epilepsy than in generalized epilepsy.

Adolescent↗
PubMed2004

Paroxysmal eyelid movements: a confusing feature of generalized photosensitive epilepsy.

BACKGROUND: Persistent, frequent, nonepileptic paroxysmal eyelid movements were observed in 19 children and adults with well-controlled generalized epilepsy. METHODS: Patients were identified from five epilepsy centers. RESULTS: Seventeen patients were female and two male. All had generalized photosensitive epilepsy requiring antiepileptic drugs (AEDs). In two children, paroxysmal eyelid movements began 2 to 4 years before their epilepsy was noted; in the remainder, it was noted when epilepsy was first diagnosed. Age at last follow-up was 8 to 38 years (average 21 years) with average follow-up of 9 years. All patients showed photosensitive generalized spike-wave discharges on EEG. Paroxysmal eyelid movements were a source of diagnostic confusion, but direct examination and video during EEG recording distinguished the attacks from absence seizures. In all cases, the epilepsy is completely or nearly completely controlled with AEDs, but the paroxysmal eyelid movements have not resolved with age. In 12 cases, there was a family history of the eyelid disorder without epilepsy. Videos of patients and an affected parent are available on the Neurology Web site. CONCLUSION: There is an association between paroxysmal eyelid movements and photosensitive generalized epilepsy, creating diagnostic confusion.

Adolescent↗
PubMed1989

Organic disorders in children with epileptic seizures.

1) Brain C-T scan was done in 1,005 epileptic children as one of the diagnostic methods, and 32% showed abnormal findings. 2) Infantile spasm showed abnormal scan most frequently at 52.9%, persistent subtle seizure 46.7%, simple partial epilepsy 37.7%, and myoclonic epilepsy 37.5%, in order of frequency. 3) In partial epilepsy the positive scan detection rate was 35.2% of the total, with simple partial epilepsy 37.7%, complex partial epilepsy 36.1% and secondary generalized epilepsy 33.5%. These rates are higher than those of generalized epilepsy (27.1%). 4) In generalized epilepsy, generalized tonic clonic showed abnormal scan in 26.1%, generalized tonic in 23.6%, generalized clonic in 20.5%, atypical absence in 15% and typical absence in none. 5) Brain tumor was detected in 2.18%. 6) Positive scan is commonly detected in seizures starting in young age group, and in epileptic patients with focal neurologic signs as well as focal EEG abnormality. 7) The curable lesions were brain tumor, some granulomas, and arachnoid cyst. 8) Brain C-T scan is an effective diagnostic method in epileptic children to identify structural abnormalities of the brain and to make sure that the abnormality does not progress, but it would be better to perform C-T scan case by case rather than as a routine diagnostic procedure.

Adolescent↗
PubMed2005

Sodium channel dysfunction in intractable childhood epilepsy with generalized tonic-clonic seizures.

Mutations in SCN1A, the gene encoding the brain voltage-gated sodium channel alpha(1) subunit (Na(V)1.1), are associated with genetic forms of epilepsy, including generalized epilepsy with febrile seizures plus (GEFS+ type 2), severe myoclonic epilepsy of infancy (SMEI) and related conditions. Several missense SCN1A mutations have been identified in probands affected by the syndrome of intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC), which bears similarity to SMEI. To test whether ICEGTC arises from molecular mechanisms similar to those involved in SMEI, we characterized eight ICEGTC missense mutations by whole-cell patch clamp recording of recombinant human SCN1A heterologously expressed in cultured mammalian cells. Two mutations (G979R and T1709I) were non-functional. The remaining alleles (T808S, V983A, N1011I, V1611F, P1632S and F1808L) exhibited measurable sodium current, but had heterogeneous biophysical phenotypes. Mutant channels exhibited lower (V983A, N1011I and F1808L), greater (T808S) or similar (V1611F and P1632S) peak sodium current densities compared with wild-type (WT) SCN1A. Three mutations (V1611F, P1632S and F1808L) displayed hyperpolarized conductance-voltage relationships, while V983A exhibited a strong depolarizing shift in the voltage dependence of activation. All mutants except T808S had hyperpolarized shifts in the voltage dependence of steady-state channel availability. Three mutants (V1611F, P1632S and F1808L) exhibited persistent sodium current ranging from approximately 1-3% of peak current amplitude that was significantly greater than WT-SCN1A. Several mutants had impaired slow inactivation, with V983A showing the most prominent effect. Finally, all of the functional alleles exhibited reduced use-dependent channel inhibition. In summary, SCN1A mutations associated with ICEGTC result in a wide spectrum of biophysical defects, including mild-to-moderate gating impairments, shifted voltage dependence and reduced use dependence. The constellation of biophysical abnormalities for some mutants is distinct from those previously observed for GEFS+ and SMEI, suggesting possible, but complex, genotype-phenotype correlations.

Alleles↗
PubMed1997

Proton magnetic resonance spectroscopic imaging for discrimination of absence and complex partial seizures.

We performed proton magnetic resonance spectroscopic imaging of the temporal lobes between, during, and soon after nonconvulsive seizures in 20 patients with documented temporal lobe epilepsy, 5 patients with primary generalized epilepsy, and 2 patients with secondary generalized epilepsy. Our objective was to determine whether there were metabolic changes observable by magnetic resonance spectroscopic imaging during seizures and whether these changes were specific for focal or generalized nonconvulsive seizures. We found a significant increase in lactate to creatine plus phosphocreatine (lactate/creatine) values, reflecting an imbalance in energy supply and demand or an adaptation in response to ictal neuronal discharges, during and soon after complex partial seizures, but not during or soon after absence seizures associated with generalized epilepsy. In patients with temporal lobe epilepsy, the N-acetylaspartate resonance relative to creatine plus phosphocreatine was low in one or both temporal lobes, indicating neuronal loss or damage. This was not observed in patients with primary generalized epilepsy. The regions with abnormal lactate/creatine and N-acetylaspartate/creatine values corresponded to the epileptogenic focus as defined by clinical-electroencephalographic investigation. There was no change in the N-acetylaspartate/creatine values in the temporal lobes between the interictal, ictal, or postictal states. We conclude that (1) partial seizures are associated with abnormally high lactate levels, but absence seizures are not, and (2) no short-term changes of N-acetylaspartate occur during or soon after complex partial seizures or absence seizures. These findings may be related to the lack of postictal confusion in patients with absence seizures, as well as with the more benign course of primary generalized epilepsy with nonconvulsive attacks.

Adolescent↗
PubMed1992

[Idiopathic epilepsy with generalized seizures in early childhood].

Idiopathic epilepsies with generalized seizures of early childhood are based on a genetic predisposition. The onset takes place between the first and fifth years of age, boys are affected more often than girls. Dependent on the clinical symptomatology you have to distinguish: myoclonic seizures; atonic-astatic seizures; myoclonic-astatic seizures; absences; tonic-clonic seizures. In more than half of the cases a combination of these seizures can be observed. The differentiation of epilepsies with generalized seizures of multifocal origin (infantile spasms, Lennox-Gastaut syndrome and Pseudo-Lennox syndrome [atypical benign epilepsy]) may be difficult but is essential. Therapy of choice is valproate, often in combination with ethosuximide (in children with minor seizures) or with kaliumbromide or phenobarbital (in children with tonic-clonic seizures). Generally the prognosis is more unfavourable if epilepsy starts in the first year of life with afebrile and febrile generalized tonic-clonic or clonic seizures, if children are suffering from longlasting states of seizures and if development is disturbed before beginning of epilepsy.

Anticonvulsants↗
PubMed1998

Seizure recurrence and risk factors after withdrawal of chronic antiepileptic therapy in children.

The aim of this study was to identify the risk factors for seizure recurrence after withdrawal of chronic antiepileptic therapy in 226 children: 136 with partial epilepsies and 90 with generalized epilepsies. The influence on prognosis of the different variables was assessed retrospectively with univariate and multivariate analysis. With a mean observation period of 5.85+/-3.87 years, seizure recurrence occurred in 24.3% of all patients with partial and generalized epilepsies. In children with partial epilepsies, the following factors were found to significantly increase relapse risk after treatment withdrawal: neurological abnormalities; interval between seizures less than 1 month at onset of illness; the use of VPA in treating seizures; start of withdrawal after 6 years of age; frontal paroxysmal activity; and abnormal EEG before drug withdrawal. In children with generalized epilepsies the risk factors were found to be: abnormal neonatal period; first seizure after 10 years of age; mean duration of seizures greater than 1 minute; poor school progress and generalized spike-waves in EEG. The factors associated with the risk of recurrence in children with generalized epilepsy appear to differ from to those related to partial epilepsies, in which seizure treatment with VPA was associated with an increased recurrence risk after the withdrawal of antiepileptic drugs.

Adolescent↗
PubMed2005

Genetic influence on the clinical characteristics and outcome of febrile seizures--a retrospective study.

PURPOSE: To assess the influence of the family history (FH) of epilepsy or febrile seizures (FSs) on the clinical presentation of FSs and on their outcome. METHODS: We reviewed the charts of 482 children admitted to the Ste-Justine Hospital with FSs between 3 months and 6 years of age and followed for at least 5 years. RESULTS: Children with a positive FH of epilepsy (n=67) showed significantly more focal and recurrent FSs than those without such a FH. The risk of developing partial epilepsy (n=17) or generalized epilepsy (n=19) was significantly greater in children with focal or recurrent FSs, respectively. In children with focal FSs, only two out of 30 (6.7%) children with a negative FH of epilepsy developed partial epilepsy compared with four out of nine (44.4%) children with a positive FH. In children with recurrent FSs, as much as seven out of 34 (20.6%) children with a positive FH of epilepsy developed generalized epilepsy compared to only eight out of 161 (0.05%) of those with a negative FH. Nevertheless, when not taking into account the clinical presentation of FSs, the positive FH of epilepsy constituted a risk factor for developing generalized but not partial epilepsy. Finally, children with a positive FH of FSs (n=120) exhibited significantly more recurrent FSs than those without such a FH, but this did not modify the risk of epilepsy. CONCLUSION: The FH of FSs and/or epilepsy should be taken into account when evaluating the risk of FSs recurrence and of epilepsy.

Child↗
PubMed2006

Familial genetic predisposition, epilepsy localization and antecedent febrile seizures.

PURPOSE: The magnitude of genetic influence in epilepsy may vary in relation to epilepsy classification and localization and factors such as antecedent febrile seizures. We assessed this genetic influence in a large epilepsy population. METHODS: Patients with established epilepsy diagnosis evaluated in the Vanderbilt Epilepsy Program were systematically questioned about family history of epilepsy and febrile seizures, prior febrile seizures and other risk factors for epilepsy. RESULTS: A total of 1994 patients with epilepsy and reliable family history were identified. Patients with prior febrile seizures (FS) were more likely to have a family history of febrile seizures than those without prior FS (p<0.000001) and also had a greater proportion of relatives with febrile seizures. The groups did not differ with respect to family history of epilepsy. Patients with generalized epilepsy were more likely to have first and second degree relatives with epilepsy than those with partial epilepsy (40.2% versus 31.2%, p=0.001), and also had a greater proportion of affected first degree relatives (p<0.000001). The proportion of first degree relatives affected with epilepsy was higher than local published prevalence, for both groups. CONCLUSION: Susceptibility for febrile seizures with subsequent epilepsy may be genetically distinct from susceptibility for afebrile seizures alone. Although family history of epilepsy was more likely with generalized epilepsy, a familial tendency was considerable in partial epilepsy.

Adolescent↗
PubMed1994

[Generalized idiopathic epilepsy in older children and adolescents].

Generalized idiopathic epilepsies starting between 12 and 18 years of age are mostly represented by juvenile myoclonic epilepsy, juvenile absence epilepsy and grand-mal on awakening. The EEG and clinical description of the seizures, the different epileptic syndromes with their therapeutics, the prognosis and the familial forms with the molecular genetic aspects are studied. The importance of the history for the positive diagnosis is emphasized, in order to display the often overlooked myoclonies occurring in the morning. Differential diagnosis concerns mostly absences which are sometimes difficult to separate from frontal seizures, and in the case of first generalized tonico-clonic seizure, partial epilepsy which needs further investigations, and the exceptional progressive myoclonic epilepsy which begins the same way, but has a totally different prognosis. Psycho-social difficulties due to epilepsy and lack of therapeutic compliance are frequent. The therapeutic results are generally good but there is a high rate of relapse after medication withdrawal.

Adolescent↗