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PubMedDate not supplied

Manganese and epilepsy: brain glutamine synthetase and liver arginase activities in genetically epilepsy prone and chronically seizured rats.

Low blood manganese (Mn2+) concentration is associated with epilepsy in humans and rats. The low Mn2+ concentration is attributed by some investigators to the seizure activity associated with the epilepsy, whereas others propose that the low Mn2+ concentration may be secondary to genetic mechanisms underlying the epilepsy. To begin to differentiate between these possibilities, Mn(2+)-binding enzymes of liver and brain (i.e., arginase and glutamine synthetase, respectively) were assayed in rats exposed to chronically induced seizures and in genetically epilepsy-prone rats (GEPRs). Chronic seizures caused a decrease in whole blood Mn2+ levels but did not affect brain Mn2+ concentrations. Arginase activity was increased in livers of rats with chronic seizure as compared with controls, but this difference was eliminated when Mn2+ was added to the assay. Brain glutamine synthetase activity was unaffected by chronic seizures, but the activity of this enzyme was significantly lower in GEPR brain than in control brain. Liver arginase activity tended to be lower in GEPRs, although the difference was not statistically significant. These data indicate that seizures affect liver arginase activity through changes in liver Mn2+ concentration, but GEPRs show abnormalities in Mn(2+)-dependent enzymes apparently independent of seizure activity.

Animals↗
PubMed1995

Sudden death in epilepsy: a study of incidence in a young cohort with epilepsy and learning difficulty.

Sudden death, often seizure related, may occur in patients with epilepsy. Population-based incidence is probably on the order of 1:1,000/year. The incidence is much higher in selected groups, however. We wished to establish the incidence of sudden unexpected death (SUD) in a young cohort with severe epilepsy and learning difficulties. The study cohort included 310 pupils with epilepsy enrolled at a special residential school between April 1970 and April 1993. The follow-up period totaling 4,135 person-years included a period of residence at the school as well as time after leaving. Age and sex standardized overall mortality ratio was 15.9 [95% confidence interval (CI) 10.6-23.0], with 20 of 28 deaths considered epilepsy related. An incidence of sudden death cases of 1:295/year was noted. All 14 sudden deaths occurred when the pupils were not under the close supervision of the school and most were unwitnessed, which has implications for prevention.

Adolescent↗
PubMed1996

Learned helplessness, attributional style, and depression in epilepsy. Bozeman Epilepsy Surgery Consortium.

PURPOSE: We wished to examine the relevance of the theory of learned helplessness in general, and attributional style in particular, to the understanding of depression among patients with epilepsy. METHODS: Patients with lateralized temporal lobe epilepsy (TLE) (right = 73, left = 70) were administered two self-report depression inventories [Beck Depression Inventory (BDI), Center for Epidemiological Studies-Depression scale (CES-D)]. Depression scores were examined in relation to a key component of the revised theory of learned helplessness (attributional style) using the Optimism/Pessimism Scale. RESULTS: Attributional style was significantly associated with increased self-reported depression and remained significant when the effects of several confounding variables were controlled [age, age at onset, laterality of TLE, sex, and method variance]. CONCLUSIONS: The results indicate that the concept of learned helplessness in general, and attributional style in particular, are related to the genesis of depression in epilepsy. Because they are known to be related to depression in the general population, and because specific techniques for intervention and prevention are available, greater consideration of learned helplessness and attributional style in the genesis of depression in epilepsy may be worthwhile.

Adult↗
PubMed2000

A multicenter randomized controlled trial on the clinical impact of therapeutic drug monitoring in patients with newly diagnosed epilepsy. The Italian TDM Study Group in Epilepsy.

PURPOSE: To assess the clinical impact of monitoring serum concentrations of antiepileptic drugs (AEDs) in patients with newly diagnosed epilepsy. METHODS: One-hundred eighty patients with partial or idiopathic generalized nonabsence epilepsy, aged 6 to 65 years, requiring initiation of treatment with carbamazepine (CBZ), valproate (VPA), phenytoin (PHT), phenobarbital (PB), or primidone (PRM) were randomly allocated to two groups according to an open, prospective parallel-group design. In one group, dosage was adjusted to achieve serum AED concentration within a target range (10-20 microg/ml for PHT, 15-40 microg/ml for PB, 4-11 microg/ml for CBZ, and 40-100 microg/ml for VPA), whereas in the other group, dosage was adjusted on clinical grounds. Patients were followed up for 24 months or until a change in therapeutic strategy was clinically indicated. RESULTS: Baseline characteristics did not differ between the two groups. Most patients with partial epilepsy were treated with CBZ, whereas generalized epilepsies were most commonly managed with PB or VPA. PHT was used only in a small minority of patients. A total of 116 patients completed 2-year follow-up, and there were no differences in exit rate from any cause between the monitored group and the control group. The proportion of assessable patients with mean serum drug levels outside the target range (mostly below range) during the first 6 months of the study was 8% in the monitored group compared with 25% in the control group (p < 0.01). There were no significant differences between the monitored group and the control group with respect to patients achieving 12-month remission (60% vs. 61%), patients remaining seizure free since initiation of treatment (38% vs. 41%), and time to first seizure or 12-month remission. Frequency of adverse effects was almost identical in the two groups. CONCLUSIONS: Only a small minority of patients were treated with PHT, the drug for which serum concentration measurements are most likely to be useful. With the AEDs most commonly used in this study, early implementation of serum AED level monitoring did not improve overall therapeutic outcome. and the majority of patients could be satisfactorily treated by adjusting dose on clinical grounds. Monitoring the serum levels of these drugs in selected patients and in special situations is likely to be more rewarding than routine measurements in a large clinic population.

Adolescent↗
PubMed1997

Feasibility and effects of nurse run clinics for patients with epilepsy in general practice: randomised controlled trial. Epilepsy Care Evaluation Group.

OBJECTIVE: To test the feasibility and effect of nurse run epilepsy clinics in primary care. DESIGN: A randomised controlled trial of nurse run clinics versus "usual care." SETTING: Six general practices in the South Thames region. SUBJECTS: 251 patients aged over 15 years who were taking anti-epileptic drugs or had a diagnosis of epilepsy and an attack in the past two years who met specified inclusion criteria and had responded to a questionnaire. MAIN OUTCOME MEASURES: Questionnaire responses and recording of key variables extracted from the clinical records before and after the intervention. RESULTS: 127 patients were randomised to a nurse run clinic, of whom 106 (83%) attended. The nurse wrote 28 letters to the general practitioners suggesting changes in epilepsy management. For this intervention group compared with the usual care group there was a highly significant improvement in the level of advice recorded as having been given on drug compliance, adverse drug effects, driving, alcohol intake, and self help groups. CONCLUSIONS: Nurse run clinics for patients with epilepsy were feasible and well attended. Such clinics can significantly improve the level of advice and drug management recorded.

Anticonvulsants↗
PubMed2006

Which electroencephalography (EEG) for epilepsy? The relative usefulness of different EEG protocols in patients with possible epilepsy.

BACKGROUND AND AIMS: Electroencephalography (EEG) is an essential investigative tool for use in young people with epilepsy. This study assesses the effects of different EEG protocols on the yield of EEG abnormalities in young people with possible new epilepsy. METHODS: 85 patients presenting to the unit underwent three EEGs with differing protocols: routine EEG (r-EEG), sleep-deprived EEG (SD-EEG), EEG carried out during drug-induced sleep (DI-EEG). The yield of EEG abnormalities was compared using each EEG protocol. RESULTS: 98 patients were recruited to the study. Of the 85 patients who completed the study, 33 (39%) showed no discernible abnormality on any of their EEG recordings. 36 patients (43%) showed generalised spike and wave during at least one EEG recording, whereas 15 (18%) had a focal discharge evident at some stage. SD-EEG had a sensitivity of 92% among these patients, whereas the sensitivity of DI-EEG and r-EEG was 58% and 44%, respectively. The difference between the yield from SD-EEG was significantly higher than that from other protocols (p < 0.001). Among the 15 patients showing focal discharges, SD-EEG provoked abnormalities in 11 (73%). r-EEG and DI-EEG each produced abnormalities in 40% and 27%, respectively. 7 patients (47%) had changes seen only after sleep deprivation. In 2 (13%), the only abnormalities were seen on r-EEG. In only 1 patient with focal discharges (7%) was the focal change noted solely after drug-induced sleep. These differences did not reach significance. CONCLUSION: EEG has an important role in the classification of epilepsies. SD-EEG is an easy and inexpensive way of increasing the yield of EEG abnormalities. Using this as the preferred protocol may help reduce the numbers of EEGs carried out in young patients presenting with epilepsy.

Adolescent↗
PubMed2002

Voxel based morphometry of grey matter abnormalities in patients with medically intractable temporal lobe epilepsy: effects of side of seizure onset and epilepsy duration.

OBJECTIVES: To investigate the use of whole brain voxel based morphometry (VBM) and stereological analysis to study brain morphology in patients with medically intractable temporal lobe epilepsy; and to determine the relation between side, duration, and age of onset of temporal lobe epilepsy, history of childhood febrile convulsions, and grey matter structure. METHODS: Three dimensional magnetic resonance images were obtained from 58 patients with left sided seizure onset (LSSO) and 58 patients with right sided seizure onset (RSSO), defined using EEG and foramen ovale recordings in the course of presurgical evaluation for temporal lobectomy. Fifty eight normal controls formed a comparison group. VBM was used to characterise whole brain grey matter concentration, while the Cavalieri method of modern design stereology in conjunction with point counting was used to estimate hippocampal and amygdala volume. Age and sex were used as confounding covariates in analyses. RESULTS: LSSO and RSSO patients showed significant reductions in volume (using stereology) and grey matter concentration (using VBM) of the hippocampus, but not of the amygdala, in the presumed epileptogenic zone when compared with controls, but hippocampal (and amygdala) volume and grey matter concentration were not related to duration or age of onset of epilepsy. LSSO and RSSO patients with a history of childhood febrile convulsions had reduced hippocampal volumes in the presumed epileptogenic zone compared with patients without such a history. Left amygdala volume was also reduced in LSSO patients with a history of childhood convulsions. VBM results indicated bilateral thalamic, prefrontal, and cerebellar GMC reduction in patients, which correlated with duration and age of onset of epilepsy. CONCLUSIONS: Hippocampal sclerosis is not necessarily the consequence of recurrent temporal lobe seizures. A major cause of hippocampal sclerosis appears to be an early aberrant neurological insult, such as childhood febrile seizures. Secondary brain abnormalities exist in regions outside the presumed epileptogenic zone and may result from recurrent seizures.

Adolescent↗
PubMed1997

Epilepsy and everyday life risks. A case-referent study: rationale, study design, and preliminary results. Risk in Epilepsy Study Group.

Despite its favorable outcome in up to 90% of patients, epilepsy is still considered to carry a higher than normal risk of morbidity and accidents. Knowledge of the everyday life risks (illnesses, accidents) in patients with epilepsy is mostly anecdotal. For these reasons, a multinational cohort study has been started in 9 European countries to investigate the incidence and number of medical events and accidents in children and adults with unprovoked epilepsy (diagnosed in the recruiting centers in the previous 10 years) and in age- and sex-matched controls (relatives or friends). The 2 groups are being followed for at least 12 months. Using patients' diaries, data are being collected regarding the number and type of illnesses and accidents, the number of medical contacts and the actions taken, the number of hospital admissions, and the total number of days off work/school. In a preliminary report on 833 patients and 833 controls, the cases reported slightly less illnesses, medical contacts, and actions taken by doctors. Accidents and related events occurred in similar proportions in the 2 groups. Based on the results of the pilot study, idiopathic, cryptogenic and remote symptomatic epilepsy may be compatible with an at least fairly normal social life.

Absenteeism↗
PubMed1999

[Epilepsies. Did you say 'epilepsy'?].

Epileptic disorders have been neglected for a long time by neurologists and practically ignored by pediatricians, satisfied with a diagnosis of infantile convulsions. Results of animal experimentation, huge progress in ancillary tests, potent antiepileptic drugs and efficacious neurosurgical procedures have considerably improved the condition of epileptic patients. However, much remains to be done. Even if numerous and varied, data given to physicians and patients are still insufficient. Stigma linked to the word epilepsy is present in many cases. It adds a supplementary burden to people who are not lacking in problems. Too often, epilepsy remains a word used in the singular, but epileptic seizure is not synonymous with epilepsy. The outcome and hence the consequences of epilepsies are quite various. A diagnosis of seizure may be difficult, and its classification not easy in all the cases. To place it in context, that is to find its causes and consequences is even more difficult. A good knowledge of epileptic disorders and efforts to use it are necessary, but one of them, or both, can be absent. This is unfortunate, because of the frequency and duration of conditions in which seizures are a symptom, and also because their outcome mostly depends on therapeutic choices. Only clinical, pragmatic aspects of the issue are considered here.

Cost of Illness↗
PubMedDate not supplied

[Mode of inheritance of idiopathic generalized non-myoclonic epilepsy in families investigated by studying members with idiopathic epilepsy with tonic-clonic crises on waking. Antioquia, Colombia].

In attempt to identify the possible role of mayor genes, multifactorial inheritance, and cohort effects in the susceptibility to idiopathic epilepsy with generalized tonic clonic seizures of the awakening type (GTCS), complex segregation analysis was performed in 196 nuclear families ascertained through affected with probands with idiopathic epilepsy with GTCS belonging to the Paisa community of Antioquia (Colombia). Models postulating no transmission, single mayor locus (dominant and recessive) only, and multifactorial component only, were rejected. The models postulating no polygenic component to transmission, and no transmission of the major effect were also rejected. Thus far, complex segregation analysis suggested that a major autosomal codominant allele together with a multifactorial component (mixed model) best explains clustering of idiopathic epilepsy with GTCS in families of the Paisa community. The deficit of transmission of heterozygotes (0.17) is compatible with the existence of epistasis acting on a major gene whose frequency was estimated to be 0.0211. Its transmission variance accounts for 81% of the susceptibility to idiopathic epilepsy with GTCS. The complementary variance (19%) is due to polygenic component.

Adolescent↗
PubMedDate not supplied

[Prognosis of epilepsy and suppression of treatment. Prognosis of epilepsy].

OBJECTIVE: On the occasion of the XXXVII Annual Meeting of the Spanish Anti-Epilepsy League we have reviewed the prognosis of epilepsy. DEVELOPMENT: The latest population studies of prognosis indicate that the long-term prognosis of epilepsy is good. Over 80% of these patients experience remission of their illness for at least three years, within nine years of diagnosis. The probability of remission is little influenced by the aetiology of the epilepsy. The mortality of epileptic patients is 2.5-3 times greater than that of the general population, adjusted for age, is markedly influenced by the aetiology and generally occurs within the first few years after diagnosis.

Adult↗
PubMedDate not supplied

[Neuroimaging in epilepsy. Advances in SPECT and PET in epilepsy].

INTRODUCTION: The incorporation of neuroimaging techniques into the protocol for localization of epileptogenous foci has considerably reduced the need for use of intracranial electrodes. DEVELOPMENT: SPECT and PET are most useful in cases of epilepsy with no cerebral morphological anomalies, in which there are therefore no changes which shown on MR. Cerebral SPECT with perfused tracers, such as 99mTc-HMPAO, 123I-MP or 99mTc-ECD, permit the study of patients during interictal and perictal phases. In the latter case, although the procedure is complex, one may observe an increase in cerebral blood flow in the epileptogenous focus in 90% of the patients. PET with FDG allows interictal study of patients, and shows reduced metabolism in the epileptogenic region. By comparison with video-EEG there are S = 84% and SP = 86% in temporal lobe epilepsy. The diagnostic efficiency of these two techniques is rather less in the localization of extratemporal foci and in multifocal epilepsies, although it is always better than with other diagnostic techniques. They have also been shown to be useful in the prognosis of functional recovery after surgery. CONCLUSION: The possibility of studying neuroreceptors may be of great use in the investigation of the etiopathogenesis of epilepsy, and thus lead to improvement in the clinical and therapeutic management of patients. With SPECT, 123I-Iomacenil and 123I-lododexetimide are used. With PET and 11C-Carfentanyl opiate receptors have been studied. With 11C-Fluomacenil one may study the cerebral distribution of the benzodiazepine receptors.

Brain↗
PubMed2000

Quality of life, epilepsy advances, and the evolving role of anticonvulsants in women with epilepsy.

In the United States, approximately 1.1 million women of childbearing age have epilepsy. Even though antiepileptic drugs (AEDs) control the seizures of about 80% of patients with epilepsy, the management of women with epilepsy (WWE) presents physicians with unique problems, ranging from the cosmetic consequences of some AEDs (e.g., changes in weight) to the seizures of catamenial epilepsy (apparently related to a relative lack of progesterone during the luteal phase of the menstrual cycle). In addition, the effectiveness of hormonal contraceptives can be reduced by enzyme-inducing AEDs. The pregnancies of WWE present a greater risk for complications: one-quarter to one-third of WWE experience an increase in seizure frequency. In addition, difficulties during labor and adverse outcomes (e.g., fetal mortality and malformations, neonatal hemorrhage, low birth weight, and developmental delay) are more likely. The practitioner must choose a course that both prevents seizures and minimizes fetal exposure to AEDs.

Anticonvulsants↗
PubMed2004

[Establishment of temporal epilepsy models and its permanent epilepsy sensitivity].

OBJECTIVE: To explore a better method to establish an animal model of temporal epilepsy in rat and study the pathological basis of permanent epilepsy sensitivity. METHODS: Kainic acid (KA) with the dosage calculated according to the body weight was injected into 30 Wistar rats' hippocampuses by stereotactic operation. Videotape recording was used to record the seizures for 8 weeks. Two rats were randomly selected to undergo craniotomy and electroencephalography and then were killed to have their brains to be taken out to undergo slicing, staining, and histological examination 6 hours, 1 days, 3 days, 5 days, 7 days, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, and 8 weeks respectively after operation. RESULTS: Thirty minutes after the rats awoke from anesthesia, wet-dog shakes, lips and head self-movements, convulsion of forelimbs and hind limbs occurred successively. The seizures were paroxysmal with increased intervals during which, however, the rats still showed sluggish. Twenty-four hours after the rats' behavior recovered to normal. Then the seizure occurred 1 approximately 3 times every week. Epileptic waves were recorded in the hippocampus, striate body, cerebral cortex, and olfactory bulb from 5 hours to 2 months after the establishment of model. CONCLUSION: The seizure pattern and pathological basis of temporal epilepsy in the rat model established by stereotactic management were almost the same as those in human beings. Stereotactic method significantly decreased the needed dosage of KA and the cost in comparison with systematic injection. Loss of hippocampus neurons and hyperplasia of gliocytes are the basis of the permanent epilepsy sensitivity in the animal model.

Animals↗
PubMed2004

[Treatment protocol for long-term anti-epilepsy drugs in adults with refractory partial epilepsy].

The primary goals of antiepileptic treatment are complete cessation of seizure without any adverse reaction. In adult refractory focal epilepsies, a rational approach is based on adequate syndromic categorization and accurate knowledge of the pharmacological properties of antiepileptic drugs, whose number has significantly increased in recent years. Since 1991 nine new antiepileptic medications have been marketed in France, i. e. by order of appearance, vigabatrin (Sabril), felbamate (Taloxa), gabapentin (Neurontin), lamotrigine (Lamictal), tiagabine (Gabitril), fosphenytoin (a water-soluble phenytoin prodrug, Prodilantin), topiramate (Epitomax), oxcarbazepine (Trileptal) and levetiracetam (Keppra). Efficacy of these new compounds in focal epilepsies is proven, and in some patients with middle-severity focal epilepsy, clinical benefit is significant. Improvement is especially significant in terms of tolerability, ease of use and reduced interaction potential. However, some of these drugs (tiagabine, topiramate) may have an unfavorable short-term tolerance profile, while others (felbamate, lamotrigine) expose patients to a potential risk of severe acute idiosyncratic reactions. Increased availability of new drugs and the fact that drug monitoring has been claimed to be of little or no value in newly-marketed drugs have paradoxically strongly complicated therapeutic options. Moreover, only a few patients with truly refractory focal epilepsy can be made seizure-free by these new compounds, and the search for more effective anticonvulsants should continue in addition with alternative therapies or surgery.

Adult↗
PubMed2005

Epilepsy and common comorbidities: improving the outpatient epilepsy encounter.

Epilepsy is a chronic disorder that has been associated with other specific health problems. Evidence from recent clinical and basic investigations indicates that aspects of cerebral dysfunction associated with a lowered seizure threshold may also predispose toward other disorders such as depression, cognitive impairment, sleep disorders, and migraine. Similarly, certain types of brain injury may also increase the risk of adverse antiepileptic drug (AED) effects. For example, a history of febrile seizures is associated with a three fold increase in the occurrence of negative psychiatric effects of two newer AEDs. Poor fitness and obesity are also reported at higher rates in epilepsy. Some comorbid conditions in epilepsy, such a depression and anxiety, may have a greater influence on subjective health status than does seizure rate. Management strategies employed in the outpatient clinic to maximize overall health outcomes should include screening and treatment for the commonly coexistent conditions in persons with epilepsy.

Comorbidity↗
PubMedDate not supplied

[GEOS (Gabitril Epilepsy Observational Study) -- Polish results of the international study of tiagabine in partial epilepsy].

BACKGROUND AND PURPOSE: Tiagabine (TGB) is a new antiepileptic drug with a unique mechanism of action, with efficacy and tolerance confirmed in many randomized, placebo-controlled add-on trials in patients with partial epilepsy. The main aim of the international GEOS study (Gabitril Epilepsy Observational Study) was to analyze the efficacy and safety of TGB as an add-on therapy in everyday clinical practice. MATERIAL AND METHODS: 260 patients from Poland (1227 in the whole study) were enrolled (mean age 35.0+/-13.7 years). 53% had symptomatic epilepsy, 25% idiopathic, 12% cryptogenic, in remaining 10% of patients the etiology of the epileptic syndrome had not been determined. 69% of patients had complex partial seizures (CPS), 60% of patients had secondary generalized tonic clonic seizures (SGTCS) and 32% of patients had simple partial seizures (SPS). The patients were observed for 12 months. RESULTS: The full study was completed by 201 (76%) of patients. The mean TGB dose received at the end of the study was 31,3+/-12 mg/day. At the end of the study, i. e. after 12 months, 75% patients with SP, 67% patients with SGTCS and 48% patients with CPS were free of seizures. 94% of patients with SPS, 92% patients with SGTCS and 91% of patients with CPS had 50% or more reduction in seizures versus baseline. TGB was well-tolerated, adverse events appeared in 14% of patients and had mild or moderate severity. CONCLUSIONS: The obtained results confirmed that TGB was effective and well-tolerated in everyday clinical practice when given as add-on therapy to patients with partial epilepsy.

Adolescent↗
PubMed2006

[Electrode grids are available for the selection of patients with refractory epilepsy for epilepsy surgery].

In 60-85% of patients with refractory epilepsy, surgical excision of that part of the brain that is considered to be responsible for the development of epileptic seizures leads to the disappearance of the attacks. In the Netherlands, 60-70 patients undergo epilepsy surgery every year; this is a small number in comparison to the number of potential candidates. Patients with medically refractory epilepsy without structural damage on the MRI or with a lesion in or near specialised areas of the cortex could also be examined and then treated surgically. It is important that such patients be referred earlier for possible surgical treatment of their epilepsy.

Anticonvulsants↗