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PubMed2004

Effect of epilepsy and antiepileptic drugs on male reproductive health.

BACKGROUND: Men with epilepsy have reduced fertility, and antiepileptic drugs may affect semen quality. Moreover, animal studies suggest that valproate (VPA) may be associated with testicular atrophy. OBJECTIVE: To evaluate reproductive function in men with epilepsy. METHODS: Sixty men with epilepsy and 41 control men were evaluated for their reproductive health. Fifteen men were taking carbamazepine (CBZ) and 18 men oxcarbazepine (OXC) for partial epilepsy, and 27 men were taking VPA for generalized epilepsy. Reproductive hormones were assayed from serum samples, semen analysis and ultrasonography of the testicles were performed, and testicular volume was calculated. RESULTS: Men on CBZ had low serum dehydroepiandrosterone sulfate concentrations (p < 0.001), and men on VPA had high concentrations of serum androstenedione (p < 0.001). The frequency of morphologically abnormal sperm was higher among CBZ-treated (p < 0.01), OXC-treated (p < 0.05), and VPA-treated men (p < 0.01) than among the control men. Moreover, both CBZ and VPA were associated with poor motility of sperm (p < 0.05). In addition, the frequency of abnormally low sperm concentration was high in men on CBZ (p < 0.001), and the frequency of any sperm abnormality was high in men on VPA (p < 0.01). The VPA-treated men with abnormal sperm had smaller testicular volumes than the control men (p = 0.003). CONCLUSIONS: CBZ, OXC, and VPA are associated with sperm abnormalities in men with epilepsy. In addition, VPA-treated men with generalized epilepsy who have abnormal sperm may have reduced testicular volume.

Adult↗
PubMed2001

Clinical spectrum of epileptic spasms associated with cortical malformation.

The spectrum of clinico-electrical characteristics of epileptic spasms associated with cortical malformation was studied in detail. The subjects were 15 patients suffering from spasms and cortical malformation demonstrated by MRI. The types of cortical malformation causing spasms were various, including hemimegalencephaly, diffuse pachygyria, focal cortical dysplasia, and polymicrogyria. Ohtahara syndrome was diagnosed in 3 patients, and West syndrome in 8. Symptomatic localization-related epilepsy preceded West syndrome in 4 patients, and a transition from Ohtahara syndrome to West syndrome was observed in one. West syndrome was followed by symptomatic generalized epilepsy including Lennox-Gastaut syndrome in 4 patients. Nine patients showed a condition which was labeled "epilepsy with partial seizures and spasms" (EPS) and characterized by the coexistence of partial seizures and spasms, and multifocal epileptic discharges on EEG. Spasms occurred only as EPS in 5 patients. EPS appeared following Ohtahara syndrome or West syndrome in 4 patients, and showed a transition to symptomatic localization-related epilepsy in 4. However, EPS did not evolve into generalized epilepsy, and persisted until the time of last follow-up in 5 patients. Therefore, the clinico-electrical pictures of patients with spasms and cortical malformation were diverse and not always limited within those of typical generalized epilepsy.

Cerebral Cortex↗
PubMedDate not supplied

[Treatment with carbamazepine of epilepsy with behavioral trouble in mentally retarded children in a medicopedagogic institution (author's transl)].

Thirty five mentally retarded girls, with epilepsy associated with behavioral troubles, were treated with carbamazepine in a medicopedagogic institution for 4 months to 7 years. Fifty percent got better, thirty percent showed a disappearance of the epileptic spells and 67% showed an aggravation of the EEG. Improvement of behavior and absence of spells are more frequent in primary generalized epilepsy as in secondary generalized epilepsy and even less frequent in secondary generalized epilepsy. Results are better in epileptics only showing tonicoclonic crises than in those with absences. They are also better in dementia epileptica than in epilepsy without dementia. The aggravation of EEG, consistent with the disappearance of epileptic crises and behavioral improvement, is most often observed in patients with epileptic absences or progressive dementia.

Adolescent↗
PubMed1995

Changes of P300 latency with age in childhood epilepsy.

Auditory event-related potentials (P300 latency; odd-ball paradigm) were examined in 129 patients with childhood epilepsies and 53 controls. The P300 latency in the patients with epilepsies (373 +/- 39.4 ms) was significantly longer than in controls (356 +/- 38.4), and the prolongation was greatest in the patients with symptomatic partial epilepsies (390 +/- 40.5), mild in those with idiopathic generalized epilepsies (370 +/- 24.3), and minimum in those with idiopathic partial epilepsies (363 +/- 28.9). Abnormal P300 latency occurred at all ages during childhood in patients with symptomatic partial epilepsies, and at older ages in patients with idiopathic generalized epilepsies. The shortening of latency with age was relatively small in patients with epilepsies compared with controls. These results suggest that the prolongation of P300 latency (i.e., existence of cognitive disturbance) displays characteristic changes with age in each epileptic syndrome.

Adolescent↗
PubMed1991

Vigabatrin in pediatric epilepsy--an open study.

The antiepileptic effect of vigabatrin in adults has been demonstrated in a number of controlled studies. In children, the effect of vigabatrin has been investigated only to a limited extent. In order to assess the long-term effect and safety of vigabatrin in patients with severe epilepsy, an open, add-on, dose-ranging study was initiated. To date, 27 children with partial epilepsy, two with generalized epilepsy, two with Lennox-Gastaut syndrome, and one with nonclassifiable epilepsy have been enrolled in the trial. Fifty-four percent of patients have experienced a greater than 50% reduction in seizure frequency, and four patients have become seizure free. A significant reduction in seizures was noted across the patient population, although patients who were recorded as seizure free at 3 and 6 months did suffer some recurrence of seizures. However, when seizures recurred, they did so at much lower frequency than recorded at the start of the study. Thirteen patients (39%) reported adverse events attributable to vigabatrin; one was immediately withdrawn from the study, and six had their vigabatrin dose reduced. No physiologic effects were noted on normal growth or clinical physical examination.

Adolescent↗
PubMed1987

Concepts of absence epilepsies: discrete syndromes or biological continuum?

There are two current approaches to the clinical conceptualization of the generalized epilepsies. The syndromic approach attempts to subdivide the patient population into relatively homogeneous groups, largely on the basis of clinical and EEG criteria. In contrast, the neurobiological approach aims to formulate a unique profile for each patient by incorporating particulars of the patient onto the background of knowledge regarding the etiologic factors important in generalized epilepsy. The value of these two approaches is discussed with regard to the dual aims of, first, improving the understanding of generalized epilepsy, and second, providing a precise diagnosis, an accurate prognosis, and optimal treatment for the patient.

Adolescent↗
PubMed2005

Reading abilities and cognitive functions of children with epilepsy: influence of epileptic syndrome.

Children with epilepsy are at risk of developing learning disorders. To explore the influence of the epileptic syndrome on reading abilities, we have compared the neuropsychological profile of 12 children with benign idiopathic epilepsy with rolandic spikes, 10 with temporal lobe epilepsy and 12 with idiopathic generalized epilepsy. Children underwent a selection of standardised tests designed to assess: oral language, reading, short-term memory, attention and behavioural adjustment. Analysis of variance was adjusted according to age of onset of the epileptic syndrome, duration of the syndrome, and performance IQ for each group. Children with temporal lobe epilepsy (TLE) had significantly lower scores for reading speed and comprehension, but epileptic variables (the age of onset of epilepsy, duration and activity of epilepsy) had influenced academic performances. In the TLE group there was a clear effect of the topography of the epileptic foci (left-side TLE vs. right-side TLE) on reading profile. Furthermore, the effect of epileptic syndromes was found in phonological, semantic and verbal working memory deficits in the TLE group. To a lesser extent children with idiopathic generalized epilepsy (IGE) also exhibit cognitive deficit. The results of the present study lend support to epilepsy-specific patterns of neuropsychological dysfunction in children that should be considered to improve remediation of academic underachievement in these populations.

Adolescent↗
PubMed2001

Vagus nerve stimulation for children and adolescents with intractable epilepsies.

BACKGROUND: Vagus nerve stimulation (VNS) has been shown to be efficacious in the treatment of patients > 12 years of age with refractory partial epilepsies and it is suggested that VNS should be considered as one of the treatment options for these patients. METHODS: Four patients had partial epilepsies and one had symptomatic generalized epilepsy. After observation of the baseline seizure frequency and the average seizure frequency for 3 months, the VNS system was implanted. Thereafter, seizure frequency, average seizure frequency of each seizure type during the month just before the evaluation, seizure severity, side effects and quality of life were recorded. RESULTS: In four of five patients, overall seizure frequency was reduced > 50% after VNS treatment. The seizure types that showed a > 50% reduction in frequency were auras, focal clonic, generalized tonic clonic seizures, astatic, versive, hypomotor, generalized tonic and generalized clonic seizures according to Lüders' classification. In two patients, as major convulsive seizures were reduced in number after VNS treatment, dialeptic seizures (non-convulsive seizure with lapse of consciousness) gradually appeared. In one patient without significant seizure reduction, quick recovery from postictal periods after generalized tonic seizure was seen after treatment. In one patient with generalized epilepsy, improvement of cognitive function was reported by his guardians. After VNS, the number of antiepileptic drugs was reduced from three to one in one patient. No significant adverse effects were noted in any patients. CONCLUSIONS: Our results suggest that VNS is well tolerated in young patients with intractable epilepsies and it may be an important non-pharmacologic treatment option for children with severe epilepsies who cannot tolerate medical therapy and/or are not candidates for epilepsy surgery.

Adolescent↗
PubMedDate not supplied

Flunarizine in therapy-resistant infantile epilepsies.

An open add-on trial with flunarizine has been carried out in 27 cases of therapy resistant infantile epilepsies: 15 partial and 12 generalized epilepsies. Etiology was an hypoxic-ischemic encephalopathy (HIE) in 13 cases, cerebral malformations in 10 cases and 4 various prenatal and perinatal cases. After a 2 months baseline period, flunarizine was given in addition to the previous therapy in a 5 mg once daily dose. A single blind versus placebo study was carried out in another series of 16 cases. Better results were found in HIE cases than in malformative cases, and in cases with perinatal HIE than in cases with prenatal hypoxic encephalopathy. The improvement in symptomatic generalized epilepsies was more evident than in symptomatic partial epilepsies. Drowsiness was the only side effect reported.

Anticonvulsants↗
PubMed2000

Precipitating factors and therapeutic outcome in epilepsy with generalized tonic-clonic seizures.

OBJECTIVES: The aim of the study was to evaluate the influence of precipitating factors and therapy on the outcome of epilepsy with generalized tonic-clonic seizures. PATIENTS AND METHODS: Retrospective analysis of data from 34 patients (mean age at seizure onset 19 years; mean duration of follow-up 9.2 years) suffering from epilepsy of either cryptogenic or remote symptomatic (n = 19), or idiopathic (n = 15) etiology. The total number of seizures in all patients was 146. RESULTS: Without treatment 97 seizures manifested during 90.5 years without treatment (1.07 seizures/year), during treatment with carbamazepine or valproate 49 seizures occurred within 224 years (0.2 seizures/year). The frequency of seizures was significantly lower during treatment. Precipitating factors were found in relation to 31% of seizures in patients with remote symptomatic or cryptogenic epilepsy, and for 51% of seizures in patients with idiopathic epilepsy. CONCLUSIONS: There was a low frequency of seizures in patients with generalized tonic-clonic seizures. Precipitating factors are common. Antiepileptic drug treatment is effective.

Adolescent↗
PubMed1999

Positron emission tomography receptor studies.

Several PET receptor ligands have been used to investigate the neurochemical basis of the epilepsies. 11C-Flumazenil binds to the central benzodiazepine receptor (cBZR)-gamma-aminobutyric acid (GABA) A receptor complex; 11C-diprenorphine, 18F-cyclofoxy, and 11C-carfentanil to opiate receptors; and 11C-Deprenyl to monoamine oxidase B. These studies should be considered alongside high-quality magnetic resonance imaging that demonstrates the structural basis of the condition. The results should be correlated with those of quantitative in vitro neuropathologic and autoradiographic studies. Idiopathic generalized epilepsy has been studied with 11C-flumazenil and 11C-diprenorphine. There is no evidence of any interictal overall abnormality of opioid receptors in idiopathic generalized epilepsy, but typical absences have been found to displace 11C-diprenorphine from the association areas of the neocortex. This finding implies that release of endogenous opioids has a role in the pathophysiologic mechanisms of typical absences in humans. In contrast, binding of 11C-flumazenil to cBZRs has been shown not to be affected by serial absences. Studies of interictal 11C-flumazenil binding in idiopathic generalized epilepsy have not given uniform results. In one investigation a slight reduction was reported in the neocortex of patients with idiopathic generalized epilepsy in comparison with patients with partial seizures. Also observed was increased benzodiazepine receptor density in the cerebellar nuclei and decreased density in the thalamus. Widespread increases in cBZRs also have been reported in cerebral neocortex, thalamus, and cerebellar cortex. In unilateral hippocampal sclerosis, reduction of binding of 11C-flumazenil has been shown to be confined to the hippocampus and to be over and above that caused by neuron loss and hippocampal atrophy. In malformations of cortical development, abnormalities of cBZRs, as demonstrated with 11C-flumazenil PET, are more extensive than the structural abnormality revealed with magnetic resonance imaging. There often are areas of increased cBZRs, a pattern that appears unique to malformations of cortical development and that may reflect both functional and structural anomalies. In patients with mesial temporal lobe epilepsy, upregulation of mu opioid receptors has been found in lateral neocortex without an overall increase of opioid receptor binding. The pathophysiologic explanation for this finding is not clear. Possibilities include up-regulation of mu receptors in response to epileptic activity and down-regulation or occupation of kappa opioid receptors. Important future developments in this field that will increase understanding of the processes that underlie the epilepsies will come from the development of further ligands, particularly tracers that are specific for excitatory amino acid receptors, the subtypes of the opioid receptors, and the GABAB receptor.

Brain↗
PubMed1985

Involvement of cortical, thalamic and midbrain reticular formation neurons in spike and wave discharges: extracellular study in feline generalized penicillin epilepsy.

Extracellular activity of single units, simultaneously recorded in cortex, thalamus, and midbrain reticular formation was investigated during feline generalized penicillin epilepsy. The firing activity of neurons recorded in the cortex was invariably and consistently enhanced in coincidence with the positive peak and the positive-negative transient of the "spike" of the spike and wave complex, and it was greatly decreased during the wave. In the nonspecific thalamic nuclei three classes of neurons were identified according to their patterns of activity during the spike and wave complex: (i) neurons behaving like cortical units, (ii) neurons with enhanced firing activity during the wave and a decreased activity during the "spike," and (iii) unmodified neurons. In the nucleus lateralis posterior neurons of the third class were not found. Most midbrain reticular neurons could be classified in the same three classes of the nonspecific thalamic nuclei; however, 11% of those units increased their activity 20 to 30 ms earlier than did the cortical units (class IV). Investigation of the activities of all these neuronal populations immediately prior to a spike and wave discharge showed that the rhythmic cycle of excitation-inhibition commenced earlier in the cortical neurons than in any other subcortical neuron. Moreover, there were some nonspecific thalamic neurons of class II with an inhibitory phase exactly coincident with the activation of class IV midbrain reticular neurons. These data suggest (i) a leading role of cortical neurons in initiating and maintaining a spike and wave burst; (ii) the involvement of a corticothalamocortical circuit in timing the bursts, and (iii) an accessory reticulothalamic loop also involved in regulating the intraburst frequency of the spike and wave complex.

Action Potentials↗
PubMed2004

Epilepsy syndrome, focus location, and treatment choice affect testicular function in men with epilepsy.

OBJECTIVE: To evaluate testicular function in men with epilepsy treated with different antiepileptic drugs (AED) vs no drugs. METHODS: Two hundred men with epilepsy (mean age 36 years) were investigated. Inclusion criteria included one or no AED, no co-medication, and no endocrine co-morbidity. Findings were compared with those from 105 healthy men (mean age 33.9 years). Luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), free testosterone (free T), and inhibin B were measured. RESULTS: One hundred seventy-eight men had focal epilepsy (117 of these had temporal lobe epilepsy [TLE]) and 22 idiopathic generalized epilepsy (IGE). Thirty-three men were not on AED; 124 men received enzyme-inducing AED. Free T was lowered in all patient subgroups, and the T/LH ratio was lowered in all groups except patients with IGE and patients receiving valproate (VPA). T was lower in patients with temporal than extratemporal focal epilepsy. Compared with TLE patients on carbamazepine (CBZ), patients treated with VPA had higher total T and lower LH values, resulting in a significantly lower T/LH ratio with CBZ. CONCLUSIONS: Epilepsy, especially TLE, adversely affects testicular endocrine function. CBZ may increase the negative effects of epilepsy on serum levels of reproductive hormones.

Adult↗
PubMed1998

Functional expression of two KvLQT1-related potassium channels responsible for an inherited idiopathic epilepsy.

Benign familial neonatal convulsions (BFNC), a class of idiopathic generalized epilepsy, is an autosomal dominantly inherited disorder of newborns. BFNC has been linked to mutations in two putative K+ channel genes, KCNQ2 and KCNQ3. Amino acid sequence comparison reveals that both genes share strong homology to KvLQT1, the potassium channel encoded by KCNQ1, which is responsible for over 50% of inherited long QT syndrome. Here we describe the cloning, functional expression, and characterization of K+ channels encoded by KCNQ2 and KCNQ3 cDNAs. Individually, expression of KCNQ2 or KCNQ3 in Xenopus oocytes elicits voltage-gated, rapidly activating K+-selective currents similar to KCNQ1. However, unlike KCNQ1, KCNQ2 and KCNQ3 currents are not augmented by coexpression with the KCNQ1 beta subunit, KCNE1 (minK, IsK). Northern blot analyses reveal that KCNQ2 and KCNQ3 exhibit similar expression patterns in different regions within the brain. Interestingly, coexpression of KCNQ2 and KCNQ3 results in a substantial synergistic increase in current amplitude. Coexpression of KCNE1 with the two channels strongly suppressed current amplitude and slowed kinetics of activation. The pharmacological and biophysical properties of the K+ currents observed in the coinjected oocytes differ somewhat from those observed after injecting either KCNQ2 or KCNQ3 by itself. The functional interaction between KCNQ2 and KCNQ3 provides a framework for understanding how mutations in either channel can cause a form of idiopathic generalized epilepsy.

Animals↗
PubMed1999

Association analysis between a Cys23Ser substitution polymorphism of the human 5-HT2c receptor gene and neuronal hyperexcitability.

Transgenic mice lacking a functional 5-HT2c receptor gene are extremely susceptible to audiogenic seizures, suggesting that 5-HT2c receptors mediate inhibition of neuronal network excitability. The present association study tested the hypothesis that a Cys23Ser substitution polymorphism within the human 5-HT2c receptor gene modulates neuronal excitability. Genotypes of the Cys23Ser polymorphism were assessed in 454 subjects of German descent, comprising: 1) 93 severely affected alcohol-dependent males with a history of alcohol withdrawal seizure or delirium, 2) 119 patients affected by an idiopathic generalized epilepsy, and 3) 242 controls. Both sexes were analyzed separately because of the X-chromosomal location of the 5-HT2c receptor gene. The allele frequencies of the Cys23Ser variants did not differ significantly between the controls and either the severely affected alcohol-dependent males (P = 0.34), or patients with idiopathic generalized epilepsy (P > 0.57). Our results suggest that the common Cys23Ser substitution polymorphism of the human 5-HT2c receptor gene does not confer susceptibility to neuronal hyperexcitability in either idiopathic generalized epilepsy or alcohol withdrawal seizure or delirium.

Adult↗
PubMed2003

Childhood absence epilepsy and febrile seizures: a family with a GABA(A) receptor mutation.

Although several genes for idiopathic epilepsies from families with simple Mendelian inheritance have been found, genes for the common idiopathic generalized epilepsies, where inheritance is complex, presently are elusive. We studied a large family with epilepsy where the two main phenotypes were childhood absence epilepsy (CAE) and febrile seizures (FS), which offered a special opportunity to identify epilepsy genes. A total of 35 family members had seizures over four generations. The phenotypes comprised typical CAE (eight individuals); FS alone (15), febrile seizures plus (FS(+)) (three); myoclonic astatic epilepsy (two); generalized epilepsy with tonic-clonic seizures alone (one); partial epilepsy (one); and unclassified epilepsy despite evaluation (two). In three remaining individuals, no information was available. FS were inherited in an autosomal dominant fashion with 75% penetrance. The inheritance of CAE in this family was not simple Mendelian, but suggestive of complex inheritance with the involvement of at least two genes. A GABA(A) receptor gamma2 subunit gene mutation on chromosome 5 segregated with FS, FS(+) and CAE, and also occurred in individuals with the other phenotypes. The clinical and molecular data suggest that the GABA(A) receptor subunit mutation alone can account for the FS phenotype. An interaction of this gene with another gene or genes is required for the CAE phenotype in this family. Linkage analysis for a putative second gene contributing to the CAE phenotype suggested possible loci on chromosomes 10, 13, 14 and 15. Examination of these loci in other absence pedigrees is warranted.

Adult↗
PubMed1994

Lennox-Gastaut syndrome in the elderly?

The Lennox-Gastaut syndrome (LGS) is an electro-clinical syndrome of early childhood that consists of mental retardation, intractable generalized epilepsy with multiple seizure types, and typical EEG findings. We report a 64-year-old woman who was referred for presurgical evaluation with a diagnosis of intractable temporal lobe epilepsy since the age of 14 years, consisting of staring and unresponsiveness, sudden falls, and generalized convulsions. The average seizure frequency was 1-4 per month. Mental status and neurological examination were normal. There was no known etiology and magnetic resonance imaging (MRI) of the brain was normal. Interictal EEG showed findings characteristic of LGS: generalized slow spike-wave complexes, multifocal sharp waves, generalized polyspikes and paroxysmal fast activity during sleep. Despite the absence of mental retardation and the presence of normal alpha rhythm, the patient fulfills most diagnostic criteria for LGS, with unusually late onset and extremely delayed diagnosis. This case illustrates the controversial nosologic boundaries of the syndrome. Prolonged EEG video monitoring may be of value even in the elderly. The LGS and other varieties of secondary generalized epilepsy should be considered in the syndromic diagnosis of epilepsy in the elderly.

Age of Onset↗