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PubMed2001

Pregnancy in women with epilepsy : preliminary results of Kerala registry of epilepsy and pregnancy.

Eighty-five women with epilepsy were followed up for reproductive functions under the registry of epilepsy and pregnancy. 32 of them had completed the pregnancy. Their mean age was 26 years and mean seizure frequency was 0.7 during current pregnancy. Nineteen of them (59.4%) had generalized epilepsy. Nine of them were not on any anti epileptic drugs (AED), 23 women were on various AEDs, 19 being on monotherapy. Only 40% of the women were taking folic acid during pregnancy. Pregnancy ended as spontaneous abortion in one patient. Nearly one third required cesarean section. Majority (87.5%) had term babies. Three (10.7%) babies had birth asphyxia. Six babies (21.4%) had low birth weight. Congenital malformations were detected in four cases (12.5%). Malformations included neural tube defects, talipes equinovarus and other minor anomalies. These babies were exposed to sodium valproate, carbamazepine or phenobarbitone. The risk of malformation was significantly greater (p<0.05) when the mother had generalized epilepsy. The odds ratio for risk of malformation was much higher with sodium valproate (6) than that with carbamazepine (1.2) or phenobarbitone (0.8). Majority of women with epilepsy had safe pregnancy and childbirth without any aggravation of epilepsy.

Adult↗
PubMed1999

The ketogenic diet for intractable epilepsy in adults: preliminary results.

PURPOSE: Little is known concerning the efficacy and adverse effects of the ketogenic diet in adults with refractory epilepsy. This review reports preliminary results in 11 adults prospectively treated with the diet who had previously failed to gain seizure control with two or more medications and/or surgery. METHODS: Eleven patients nine women, two men), median age, 32.2 years (range, 19-45 years) were treated with the ketogenic diet with a 4:1 ratio with fluid restriction. Six patients had symptomatic partial epilepsy, and five had symptomatic generalized epilepsy. The diet was administered in addition to antiepileptic medication by a multidisciplinary team geared exclusively to adult patients. Medications were not changed while on the diet. Seizure frequency at 8-month follow-up was compared with frequency during a baseline period. RESULTS: At 8 months of follow-up, three patients had a 90% seizure decrease, three patients had a 50-89% decrease in seizure frequency, one patient had <50% seizure decrease, and four patients discontinued the diet. Of the four patients who discontinued the diet, two had no appreciable change in their seizures despite high ketone levels. Two patients were unable to maintain persistent ketosis at home, despite having done so in the hospital. All seizure types responded to the diet. Common adverse effects included constipation and menstrual irregularities in women. Most patients reported a subjective improvement in concentration. Serum cholesterol and triglycerides increased while on the diet as well as cholesterol high-density lipoprotein (HDL) ratios. CONCLUSIONS: The ketogenic diet shows promise in both adult generalized and partial epilepsy. Persistent ketosis was possible in adults, and the diet was tolerable for most patients. Further study assessing the efficacy of the ketogenic diet, and the cognitive and long-term effects is ongoing.

Adult↗
PubMed1991

[Site and propagation of focal epileptic activity: multichannel MEG/EEG analysis].

Electrophysiological examinations provide the basis for a deeper pathophysiological understanding of focal epileptic activity. In addition to electroencephalography, magnetoencephalography from field measurements is now available for biomagnetic diagnosis. As magnetoencephalography (MEG) is basically better suited for the localization of focal epileptic activity than EEG, an increase in MEG measurements has taken place over the last years. In this study we discuss magnetic source localization which was combined with anatomical 3-D-MR-images and compared with the results of EEG-registration carried out simultaneously and with other investigative procedures of presurgical diagnosis. The results of investigation show that simultaneous magnetic field measurements over one hemisphere of the skull allow localization of sources both in the temporal lobe and in deeper areas of the brain. Furthermore, propagation of epileptic activity can be registered not only in neighbouring areas of the epileptogenic source but also in regions localized deeper in the temporal lobe. This opens new possibilities for presurgical evaluation as well as an understanding of partial and generalized epilepsies. The results of investigation show primary focal epileptic activity neocortex laterally or surrounding a mesio-temporal lesion in all investigated patients with partial (temporal, frontal) and secondary generalized epilepsies. Furthermore, a pattern of propagation of focal epileptic activity which is directed from neocortical-lateral to mediobasal-limbic brain structures is found in most of these patients.

Brain Diseases↗
PubMedDate not supplied

[Clinical features of epilepsy in adolescents].

OBJECTIVE: The epilepsy is a common neurologic disorder in adolescence. Its prevalence is 1.5-2% in these ages. In this work the different epileptic types and syndromes that begin in adolescence are reviewed. DEVELOPMENT: Primary generalized epilepsies are the most frequent group. Its three syndromes, juvenile absences epilepsy, juvenile myoclonic epilepsy and epilepsy with generalized with tonic-clonic seizures on awakening, have different clinical and electroencephalographic characteristic but also share a considerable overlapping among them. The partial epilepsies are frequently functional or idiopathic, but not so often as in childhood. The secondary generalized epilepsies are rare, and among them, the progressive myoclonic epilepsies are the main group. The clinical aspects of the different disorders are described. CONCLUSIONS: 19% of epilepsies have the onset in adolescence. There is a wide spectrum of clinical syndromes, with different symptoms and prognosis and also different of the corresponding syndromes that begin in childhood.

Adolescent↗
PubMed2004

Magnetic resonance and biochemical studies during pentylenetetrazole-kindling development: the relationship between nitric oxide, neuronal nitric oxide synthase and seizures.

The major aim of this study was to elucidate the role of nitric oxide (NO) in the development of pentylenetetrazole (PTZ)-kindling as an animal model of primary generalized epilepsy. The daily administration of PTZ is associated with an increase in the amount of neuronal nitric oxide synthase (nNOS). NO generation was measured directly by in vivo and ex vivo electron paramagnetic resonance on rodents undergoing progressive convulsions. We found that primary generalized epilepsy is caused by NO induction during the persistent up-regulation of nNOS expression, but that NO induction is not associated with severe generalized seizures following long-term kindling phenomena after PTZ withdrawal. Morphological changes in the brain structure of rats were measured by magnetic resonance imaging during epileptic convulsions induced by repetitive administration of PTZ. Cerebellum volume for kindled rats decreased 20% but not in rats treated with the nNOS inhibitor, 3Br-7NI, suggesting that generation of NO in the cerebellum is related to decrease in cerebellum volume following PTZ-kindling.

Analysis of Variance↗
PubMedDate not supplied

Anticonvulsant effects of calcium channel blockers in partial and generalized model epilepsies.

The calcium channel blockers D890 and verapamil reduced neuronal calcium currents in single snail neurons with intra- and extracellular applications, respectively. Epileptic discharges of single neurons in the rat's motor cortex (in vivo) were depressed in amplitude by intracellular injection of D890. Focal seizure discharges and generalized tonic-clonic seizure activity in the cerebral cortex of the rat were reduced by intracerebroventricular perfusion of verapamil. In non-epileptic rats verapamil failed to exert a depressive effect on somatosensory evoked potentials and on the waves of the spontaneous EEG.

Animals↗
PubMed2003

The genetics of human epilepsy.

In recent years genetic discoveries have shown the central role of ion channels in the pathophysiology of idiopathic epilepsies. Uncommon epilepsy syndromes that have monogenic inheritance are associated with mutations in genes that encode subunits of voltage-gated and ligand-gated ion channels. For voltage-gated ion channels, mutations of Na(+), K(+) and Cl(-) channels are associated with forms of generalized epilepsy and infantile seizure syndromes. Ligand-gated ion channels, such as nicotinic acetylcholine receptors and GABA receptor subunits, are associated with specific syndromes of frontal and generalized epilepsies, respectively. Striking features are the variable epilepsy phenotypes that are associated with the known gene mutations and the genetic heterogeneity that underlies all known monogenic syndromes. Mutations in two genes that do not encode ion channels have been identified in the idiopathic human epilepsies. The heterogeneity of mutations described to date has precluded the development of simple diagnostic tests, but advances in the next few years are likely to have an impact on both the clinical diagnosis and the treatment of epilepsies.

Calcium Channels↗
PubMed1992

University students with epilepsy: a study of social aspects.

Improved control of epilepsy has permitted an increasing number of young persons with epilepsy to attend university. This study was designed to assess the impact of epilepsy on their education, employment, family and social life. We studied fifteen randomly selected full time university students, aged 20-28 years, who had a well documented history of partial or generalized epilepsy. One third still had seizures, over 90% were taking antiepileptic medication and all were followed by a neurologist. Interviews were conducted according to a standard open-ended questionnaire lasting 1.5 hours. After an initial adjustment period, most did not feel that epilepsy constituted a handicap to their education. They learned about epilepsy, did independent research and one quarter chose careers in the health sciences. Most reported occasional negative experiences, but were reluctant to interpret this as evidence of discrimination. All felt that they had had equal opportunities at school and at work. They were selective about imparting knowledge about their seizures to students, staff and employers, but did not hide their epilepsy. Subjects had high vocational aspirations and academic motivation reflecting good intelligence and previous educational achievements. Their positive attitude, enthusiasm and denial of difficulties were striking. This reflects improved seizure control as well as family and social support in this group of young people.

Activities of Daily Living↗
PubMed2002

Inhibition of membrane Na+-K+ ATPase activity: a common pathway in central nervous system disorders.

OBJECTIVES: The study was conducted to assess the role of hypothalamic digoxin in neuropsychiatric and systemic disorders. A hypothesis regarding the central role of hypothalamic digoxin in neuroimmunoendocrine integration is proposed. METHODOLOGY: Blood samples from patients of CNS glioma, multiple sclerosis, systemic lupus erythematosis, subacute sclerosing panencephalitis, primary generalized epilepsy, Parkinson's disease, Down syndrome, AIDS dementia with neuropsychiatric features, syndrome X with multiple lacunar state, senile dementia, familial group (a family with familial coexistence of schizophrenia, Parkinson's disease, primary generalized epilepsy, malignant neoplasia, rheumatoid arthritis and syndrome X over three generations), schizophrenia and manic depressive psychosis were analysed for RBC membrane Na+-K+ ATPase, levels of digoxin and Mg++. RESULTS: Inhibition of RBC membrane Na+-K+ ATPase activity was observed in most cases along with increase in the levels of serum digoxin and decrease in the level of serum Mg++. CONCLUSION: The decreased Na+-K+ ATPase activity can be due to increased digoxin, which is a potent inhibitor of this enzyme. The inhibition of Na+-K+ ATPase can contribute to increase in intracellular calcium and decrease in magnesium, which can result in 1) defective neurotransmitter transport mechanism, 2) neuronal degeneration and apoptosis, 3) mitochondrial dysfunction, 4) defective golgi body function and protein processing dysfunction, 5) immune dysfunction and oncogenesis. The mechanism of how increased intracellular calcium and decreased magnesium can contribute to the above effects is discussed.

Adult↗
PubMed2006

Predictors of neuropsychological impairment in seizure-free epilepsy patients.

Persons with epilepsy are at increased risk of cognitive deficits as a result of various factors like etiology, structural brain lesions, seizure frequency, seizure type, age at onset of epilepsy, hereditary factors, psychosocial factors, and possible adverse effects of antiepileptic drugs (AEDs). Despite the fact that the majority of epilepsy patients are seizure-free, previous studies on the relationship between epilepsy-related variables and cognitive function have mainly been conducted on patients with persisting seizures. In this study 158 adults with epilepsy on AED monotherapy and without epileptic seizures for at least 2 years were investigated with a neuropsychological test battery in addition to a neurological examination, MRI and EEG. The major findings were that the group had education and employment status similar to the population mean and neuropsychological function in the normal range. In the patient group without idiopathic generalized epilepsy known cerebral etiology was found to be a highly significant predictor of neuropsychological deficit. For patients with idiopathic generalized epilepsy, early seizure debut at < or =18 years was a powerful predictor of neuropsychological impairment.

Adult↗
PubMed2004

[Molecular genetics of epilepsy].

Recent identifications of genes responsible for epilepsies are now contributing to diagnosis and treatment. Mutations of voltage-gated sodium channel genes SCN1A and SCN2A have been reported in epilepsies with a variety of phenotypes including generalized epilepsy with febrile seizures plus (GEFS +), severe myoclonic epilepsy in infancy (SMEI), intractable childhood epilepsy with generalized tonic-clonic seizures (ICEGTC), and benign familial neonatal-infantile seizures (BFNIS). We also identified a sporadic nonsense mutation of SCN2A in a patient with intractable epilepsy with severe mental decline. Lafora's disease (LD) is a fatal autosomal recessive epilepsy characterized by stimuli sensitive myoclonus, grand mal seizures, and progressive intellectual and neurological deterioration. The EPM2A gene has been reported to be responsible for LD. We found multiple disease mutations of EPM2A in LD patients, and also identified a subclass of LD who shows an early onset cognitive defect and correlated with EPM2A exon 1 mutations. We reported that the laforin protein encoded by the EPM2A gene has a dual-specificity phosphatase activity, associates with polyribosome, and interacts with the HIRIP5 protein with NifU-like domain. We recently generated and reported the EPM2A KO mice those develop neurodegeneration and other features similar to those of LD patients.

Child↗
PubMedDate not supplied

[Value and limits of C.T. scan in neurologics diseases in infancy and childhood (author's transl)].

The results obtained in 151 children who underwent C.T. scan at the Pediatric Department of the University of Padova are reported. The high incidence of negative or aspecific results in the cases of static encephalopathy, in primary generalized epilepsy and in acute diffuse cerebral infectious process is emphasized. C.T. confirmed its high diagnostic value in tuberous sclerosis and cerebral abscess. While non providing the precise diagnosis it may be helpful in some demyelinating diseases. In secondary generalized epilepsy and in partial epilepsy C.T. scan may suggest the prognosis and a possible surgical approach. On the basis of these results and of other published reports a greater selectivity in the use of C.T. is strongly recommended.

Atrophy↗
PubMed1983

The density of dystopic neurons in the white matter of the gyrus frontalis inferior in epilepsies.

It has been suspected for a long time that developmental disturbances of the brain could be a factor in the causation of epilepsies. The diagnostic term "microdysgenesis" indicates the morphological correlate for this hypothesis. An increase in the number of nerve cells in the white matter belongs to this microdysgenesis. Its diagnosis, judged purely qualitatively, is very uncertain and cannot be clearly be differentiated from normal findings. In this study, the nerve cell density in the white matter of the gyrus frontalis inferior was determined morphometrically. There was a significantly increased cell count in the group with primary generalized epilepsy compared to the control group. However, even in the group with traumatic epilepsy there still a significantly higher cell count than in the control group, although clearly lower than in the group with primary generalized epilepsy. The study supports the hypothesis that disturbed maturation could be an aetiological factor in epilepsy.

Adult↗
PubMed1978

[Valproic acid in the treatment of epilepsy with special emphasis on serum level determination (author's transl)].

Valproic acid has become a regular component of antiepileptic therapy. Generally it is used against genetically caused, primary generalized epilepsies with bilateral hypersynchronous neuronal discharges in the EEG. An improvement can also be observed by Valproic acid-treatment for secondary generalized and partial epilepsies. Therapeutic results could possibly be improved through a consideration of the serum concentration of valproic acid. Some of the commercial preparations contain the sodium salt of Valproic acid. The free acid which is quickly absorbed, is released in the stomach (tablet) or in the intestine (dragee). The half life is about 15 to 17 hours (one finds a range of 6 to 20 hours in the literature). In view of the half life, it is recommended that the daily dose should be divided into three single doses. About 84 to 95% of the substance is protein bound. Up to now, clinically relevant observations concerning the displacement of valproic acid from its protein binding are unknown. Recently in in vitro studies a decreased protein binding of valproic acid due to phenylbutazone, salicylic acid, and sulfadimethoxine and vice versa, a displacement of phenobarbital and phenytoin caused by valproic acid could be demonstrated. The therapeutic range of the serum level was between 50 and 120 mcg/ml. Individual patients showed that the dispensed dose did not reliably yield the expected serum levels. The necessary daily dose lies for adults between 600 and 2400 mg, in children between 15 and 150 mg/kg. The wide range of allowable dosis is dependent on whether or not valproic acid is to be given in conjunction with other antiepileptic drugs. When phenobarbital and valproic acid are given in conjunction one should be alert for a rise in the phenobarbital serum level. Results of studies in which valproic acid was combined with several other antiepileptic and psychotropic drugs are reported. The majority of the researchers determine a clear parallelism between clinical improvement and a normalization of the EEG in primary generalized epilepsies with bilateral synchronous 3/sec. spikes and waves. The background activity, determined by visual inspection, is not affected. Few workers discuss the correlation of the side effects of valproic acid and its serum level. Tiredness and impaired function of thrombocytes has been observed to be dependent on the valproic acid plasma level.

Blood Platelets↗
PubMed2005

The clinical spectrum and natural history of gelastic epilepsy-hypothalamic hamartoma syndrome.

PURPOSE: To delineate the clinical spectrum and patterns of evolution of epilepsy with gelastic seizures related to hypothalamic hamartoma (HH). PATIENTS AND METHODS: We evaluated patients with HH, observed between 1986 and 2002 for whom at least one ictal video-EEG or EEG recording of gelastic seizures was available. RESULTS: Six subjects (four male, two female) with sessile HH between 0.8 and 1.7 cm in diameter were identified. The onset of gelastic seizures was between 2 months and 20 years. It evolved to secondary generalized epilepsy in one case, and to drug-resistant partial epilepsy in the other five from 2 to 13 years after onset. No patient showed precocious puberty. Severe cognitive impairment developed in the patient with secondary generalized epilepsy, and a mild cognitive defect in two others. Patients with an HH below 1cm did not show neuropsychological or behavioural disturbances. Drug resistance occurred in all cases. Surgical removal of HH markedly improved the clinical evolution in two patients. CONCLUSIONS: Gelastic epilepsy-HH syndrome can differ in severity and evolution. A catastrophic evolution and drug resistance can be reversed by surgical or by gamma-knife ablation of HH.

Adult↗
PubMed1995

Ovulatory function in epilepsy.

Women with epilepsy have lower fertility rates than women without epilepsy. We hypothesized that limbic dysfunction in temporal lobe epilepsy (TLE) alters the release of hypothalamic trophic hormones that secondarily affect release of the pituitary gonadotropins, causing ovulatory failure. We assessed ovulatory function over three consecutive menstrual cycles in 17 women with partial seizures arising from the temporal lobe (TLE), 7 women with primary generalized epilepsy (PGE), and 12 controls. We devised scores to reflect ovulatory function that were based on daily basal body temperature and monthly serum progesterone levels. Seizure frequency, antiepileptic drugs (AEDs), and depressive symptomatology were also evaluated. Anovulation was more frequent in subjects with TLE (35.3%) than in subjects with PGE (0%) or in controls (8.3%). Anovulatory cycles tended to occur more frequently in subjects with TLE who were treated with polytherapy than in those receiving monotherapy, but this result was not statistically significant. Seizure frequency and symptoms of depression did not affect ovulatory function. Although AED polytherapy may increase the likelihood of anovulation, our results suggest a mechanism of infertility related to temporal lobe dysfunction.

Adolescent↗
PubMed1995

[Vigabatrin and lamotrigin: experiences with 2 new anticonvulsants in the Swiss epilepsy clinic].

Vigabatrin and lamotrigine are two new antiepileptic drugs which have recently become available. Vigabatrin is a specific and irreversible inhibitor of the enzyme gamma-amino-butyric-acid (GABA) transferase. Its administration leads to a long lasting increase in GABA, the most important inhibitory neurotransmitter. Vigabatrin is effective in both adults and children in the treatment of partial and especially complex-partial seizures. After add-on in vigabatrin to their therapeutic drug regime in 116 of our own patients, 39% of previously therapy resistant patients reported a reduced seizure frequency of at least 50% and 6% of them became seizure free. In secondarily generalized epilepsies the best results were observed in axial (infantile) spasms. In addition there was some improvement in tonic and convulsive seizures. Single patients showed increased myoclonic and clonic seizures. Initial efficacy was not always maintained during follow-up. In the experience of other authors, vigabatrin is also effective in the treatment of infantile spasms. It is not suitable for the treatment of generalized epilepsies with absences and myoclonic seizures. Most patients tolerate vigabatrin very well, although psychotic episodes are sometimes reported. So far there have been no relevant hepatic or hematological side effects. Lamotrigine is also effective in the treatment of partial seizures, for which it is approved. However, uncontrolled studies and our own experience have shown that it is even more effective in generalized seizures. As add-on therapy in absences and tonic or tonic-clonic seizures, a significant reduction in seizure frequency--in individual cases seizure freedom--can be achieved.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminobutyrate Transaminase↗