When should the pre-operative study of epileptic patients be carried out?

There is great controversy as to the best moment for the preoperative study of patients with intractable epilepsy. In this study we attempt to give an answer to this question based on a review of the literature and personal experience. First various problems are analyzed: the epilepsy-lesion relationship; kinds of treatment and types of epilepsy: the concept of curative or palliative surgery, surgical syndromes, how long epilepsy has been present and the age of the patient at the time of operation. With these factors in mind we attempt to analyze the clinical situations and determine in each cases the optimum time to carry out any possible surgical treatment as a complement or 'part' of the medical treatment of these patients as a whole.     

Treatment of warts with topical pyruvic acid: with and without added 5-fluorouracil

Numerous studies have suggested that epilepsy and asthma may be related conditions. There has, however, been little epidemiologic data published to support this association. We conducted a retrospective study to determine whether the prevalence of epilepsy is increased among children with asthma, and the prevalence of asthma is increased among children with epilepsy, in comparison with the general pediatric population. We reviewed the medical records, at a large city hospital, of two groups of pediatric outpatients: (1) 400 consecutive patients with asthma followed regularly at the asthma and allergy clinic; and (2) 201 consecutive patients with idiopathic epilepsy followed regularly at the pediatric neurology clinic. Patients with a history of birth prior to 36 weeks' gestational age were excluded. Among the 400 cases of asthma, there were three patients with idiopathic epilepsy (prevalence of 0.75%). The prevalence of epilepsy was similar in mild (0.79%) and moderate-to-severe (0.73%) asthma. Among the 201 cases of idiopathic epilepsy, there were 12 patients with asthma (prevalence of 5.97%). Similar percentages of epilepsy patients with and without asthma reported generalized tonic-clonic, complex partial, simple partial, and myoclonic seizures as their predominant type. The prevalence values in this study are consistent with the prevalence of epilepsy and asthma in the general pediatric population. Our findings therefore suggest that idiopathic epilepsy and asthma are not etiologically related or mutually predisposing conditions. Small samples, failure to exclude patients born prematurely, and the equation of electroencephalographic (EEG) abnormalities with epilepsy may account for the results of previous studies.     

Legal aspects of epilepsy and coexisting psychiatric disorders

Major advances in understanding the neurobiology of epilepsy have led to more precise diagnosis, early rational treatment with new drugs, useful new neurosurgical techniques, etc. This has led to significant control of seizures, a marked reduction in concurrent psychopathology, improved quality of life of the epileptic patient, the almost complete abolition of old-style institutions for these patients, etc. However in spite of greater scientific knowledge about epilepsy, this has not led to an equally great advance socially. Old-fashioned restrictions and limitations based on mistaken ideas as to the nature of epilepsy still remain. Epilepsy is still considered in the same light as the psychopathological disorders seen in some epileptics, as a result of different variables which are not necessarily related to seizures. Current legal rulings on epilepsy, with or without co-existing mental disorder, are reviewed in relation to their effect on driving motor vehicles, carrying out military service, the condition of minusvalia, the possibility of legal incompetence, and the nullity of marriage and of priesthood. It is concluded that although the limitations maintained by some statutory requirements are reasonable, it would be fairest to abolish restrictions which, in view of present scientific knowledge, are out of date and prevent the return to normal and full social integration which should prevail for people with epilepsy.     

Attention problems in epilepsy: possible significance of the epileptogenic focus

Investigation of the relation between epilepsy and cognition presents serious methodologic problems because several factors may contribute to impair neuropsychological performances in epileptic persons. Benign epilepsy of childhood with rolandic paroxysmal discharges (EPR) may be a very useful model of investigation in relation to opportunity to examine subjects without brain damage, therapy, and negative environmental influences. Thus, neuropsychological dysfunction in patients with EPR may support the hypothesis that epilepsy itself plays a specific role in the genesis of cognitive disturbances. We assessed the impact of the laterality of the epileptogenic focus on cognition of children with EPR. All subjects performed a figure cancellation task, a test used to evaluate mainly attention mechanisms and abilities in processing visuospatial information. Results showed that children with right-sided (or bilateral) focus scored worse, whereas children with left-sided focus performed as well as the control subjects. Our data agree with those of studies suggesting that focal discharges may be related to poor cognitive performance. Evidence of a concordance between neurophysiologic and neuropsychologic findings may have great practical and theoretical implications in management of epileptic patients.     

Quantitative MRI in outpatient childhood epilepsy

PURPOSE: In adult studies, MRI volumetrics is a proven technique in presurgical assessment of epilepsy. Hippocampal volume loss is maximal in the syndrome of mesial temporal lobe epilepsy. We aimed (a) to validate this methodology in a pediatric outpatient epilepsy population (b) to determine the relationship of hippocampal asymmetry (HA) to epileptic syndromes and risk factors. METHODS: Two neurologists classified the epileptic syndrome in 79 pediatric outpatients, according to the International Classification of Epilepsies and Epileptic Syndromes (ILAE). Hippocampal volumetrics were performed in all patients. HA was defined according to adult control values. RESULTS: Inter-rater variability on measurement of HA was very small (Correlation of test retest of 0.97 on 17 children <3 years old). The rate of HA was 44/79 (57%). In 21 patients, (27%) potentially epileptogenic lesions (other than HA) were identified (cerebral dysgenesis n = 11). HA was present in 9/15 (60%) of temporal lobe epilepsy and in 15/28 (54%) extratemporal onset epilepsy and 5/11 (46%) of generalized symptomatic epilepsy. Analysis confined to <13 years also showed HA was not specific for epileptic syndrome. There was no significant association of febrile convulsions (13%) with HA or temporal lobe epilepsy. CONCLUSIONS: There is a high incidence of HA in childhood epilepsy. HA was not confined to clinically defined temporal lobe epilepsy. The poor correlation of epileptic syndrome to quantitative MRI findings may be due to the inadequacies of epilepsy classification in the younger child, with the clinical semiology providing misleading localizing information. Normative childhood data for hippocampal volumes and symmetry is needed.     

Neuropsychologie de l'épilepsie infantile.

From a neuropsychological standpoint, epilepsy is a very heterogeneous condition. Epilepsies are divided into two categories (focal and generalized) that are differentiated by the neuropsychological symptoms that are present. Cognitive difficulties present in children suffering from focal epilepsy are usually specific to the cerebral area involved, while generalized epilepsies are linked to a diffuse neuropsychological deficit profile as well as to a more limited intellectual functioning. The aim of this article was to establish a neuropsychological profile of the various syndromes of focal and generalized epilepsy, and to outline the psychological and social effects of epilepsy among children with this condition. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pregnancies of women with epilepsy: a population-based study in Iceland

PURPOSE: Women with epilepsy who become pregnant are commonly considered to be at high risk for complications during pregnancy or delivery. The offspring are also considered to have increased risk of perinatal mortality, congenital malformations, and maturational delay. Because few of these studies are population based, potential bias exists because of selection. METHODS: We performed a historical population-based cohort study in Iceland to determine the prevalence of epilepsy among pregnant women, to identify pregnancy and delivery complications in women with epilepsy, and to determine the outcome of their pregnancies as compared with that in the general population of Iceland. We identified all women with active epilepsy who gave birth during a 19-year period in Iceland. RESULTS: In this population, 3.3 in 1,000 pregnancies involve mothers with active epilepsy. The frequency of adverse events (AE) during pregnancy in the women with epilepsy is similar to that observed among all live births in the population, but cesarean section was performed twice as frequently as in the general population. Perinatal mortality rate and mean birth weight are not significantly different in the offspring of women with epilepsy as compared with rest of the population. The risk of major congenital malformations (MGM) is increased 2.7-fold over that expected when a mother is treated with antiepileptic drugs (AEDs) during a pregnancy. CONCLUSIONS: Our study indicates that the rate of complications of pregnancy in mothers with active epilepsy is low and similar to that of the general population with epilepsy. Use of AEDs by the mother during pregnancy significantly increases the risk of MGM in the offspring.     

A study of apoptosis in human glomerulonephritis as determined by in situ non-radioactive labelling of DNA strand breaks

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

NMDA receptor activation during status epilepticus is required for the development of epilepsy

NMDA receptor activation has been implicated in modulating seizure activity; however, its complete role in the development of epilepsy is unknown. The pilocarpine model of limbic epilepsy involves inducing status epilepticus (SE) with the subsequent development of spontaneous recurrent seizures (SRSs) and is widely accepted as a model of limbic epilepsy in humans. The pilocarpine model of epilepsy provides a tool for looking at the molecular signals triggered by SE that are responsible for the development of epilepsy. In this study, we wanted to examine the role of NMDA receptor activation on the development of epilepsy using the pilocarpine model. Pretreatment with the NMDA receptor antagonist MK-801 does not block the onset of SE in the pilocarpine model. Thus, we could compare animals that experience similar lengths of SE in the presence or absence of NMDA receptor activation. Animals treated with MK-801 (4 mg/kg) 20 min prior to pilocarpine (350 mg/kg) (MK-Pilo) were compared to the pilocarpine treated epileptic animals 3-8 weeks after the initial episode of SE. The pilocarpine-treated animals displayed both ictal activity and interictal spikes on EEG analysis, whereas MK-801-pilocarpine and control animals only exhibited normal background EEG patterns. In addition, MK-801-pilocarpine animals did not exhibit any SRSs, while pilocarpine-treated animals exhibited 4.8 +/- 1 seizures per 40 h. MK-801-pilocarpine animals did not demonstrate any decrease in pyramidal cell number in the CA1 subfield of the hippocampus, while pilocarpine animals averaged 15% decrease in cell number. In summary, the MK-801-pilocarpine animals exhibited a number of characteristics similar to control animals and were statistically significantly different from pilocarpine-treated animals. Thus, NMDA receptor inhibition by MK-801 prevented the development of epilepsy and interictal activity following SE. These results indicate that NMDA receptor activation is required for epileptogenesis following SE in this model of limbic epilepsy.     

Vascular determinants of epilepsy: the Rotterdam Study

PURPOSE: To investigate the relation between vascular determinants and epilepsy in an elderly population. METHODS: This is a cross-sectional, community-based, case-control study. The total study population was comprised of 4,944 subjects, 65 of whom had epilepsy which conformed to International League Against Epilepsy (ILAE) criteria. Vascular determinants that were evaluated included a history of stroke or myocardial infarction, peripheral vascular disease, hypertension, serum total cholesterol and left ventricular hypertrophy. Multivariate logistic regression analysis was used to calculate prevalence odds ratios (OR), adjusted for age and gender, as a measure of the strength of the associations. RESULTS: A history of stroke was strongly associated with lifetime epilepsy (OR 3.3; 95% CI [Confidence Interval] 1.3-8.5), as well as with late-onset epilepsy (OR 3.1; 95% CI 0.9-10.6). All vascular determinants were associated with lifetime epilepsy and late-onset epilepsy, with odds ratios >1. When stroke patients were excluded, the odds ratios were statistically significant for the relationships between total cholesterol and late-onset epilepsy (OR 1.3, 95% CI 1.0-1.6) and left ventricular hypertrophy and late-onset epilepsy (OR 2.9, 95% CI 1.0-8.6). Furthermore, presence of any of these vascular indicators was twice as common among subjects with late-onset epilepsy as compared with subjects without epilepsy (OR 2.0, 95% CI 0.9-4.2), and this was statistically significant when stroke patients were excluded (OR 2.1, 95% CI 1.0-4.7). CONCLUSIONS: These results suggest that there may be a relationship between vascular factors and the risk of late-onset epilepsy, apart from the relationship that exists through clinically overt stroke.     

Incidence of photosensitive epilepsy: a prospective national study

We undertook a prospective nationwide study to determine the incidence of photosensitive epilepsy (PE). Virtually all EEG departments in Great Britain (providing approximately 90% coverage of all EEGs performed on people with newly diagnosed seizures) screened cases referred to them over a 3 month period and identified all new cases of epilepsy (defined as one or more recognised seizures) whose first EEG showed a photoparoxysmal response (PPR) on intermittent photic stimulation (IPS). 191 cases were identified, 143 of whom had type 4 PPRs (generalised spike and wave on IPS) on their first EEG. The annual incidence of cases of epilepsy with type 4 PPRs on their first EEG was conservatively estimated to be 1.1 per 100,000, representing approximately 2% of all new cases of epilepsy. When restricted to the age range 7-19 years, the annual incidence rose to 5.7 per 100,000-approximately 10% of all new cases of epilepsy presenting in this age range. To ascertain if there was a significant seasonal variation in PE, 5 EEG departments (which together contributed 15% of cases in the first study period) were visited during a second 3 month study period to identify all new cases of epilepsy with type 4 PPRs on their first EEG. No significant seasonal variation in incidence between summer and winter was found.     

Epilepsy and the heart

The relations between epilepsy and heart are complex and expressed in two opposite sides. (1) Cardiac arrhythmias may provoke epileptic seizures but these seizures are, in this case, syncopal attacks. Nevertheless, in the past, these clinical features have been individualized as "cardiac epilepsy" or epilepsy in cardiacs. However, true epileptic seizures could be observed in the course of a syncopal attack and a syncope may complicate the issue of an epileptic seizure. (2) On the other hand, epileptic seizures may provoke severe cardiac arrhythmias. The incidence rate of sudden death in patients with epilepsy is estimated to be 1/1000 patients. The exact neural mechanisms in cardiac arrhythmias seizures could explain only some of the sudden unexpected deaths observed in epileptic patients. The role of antiepileptic drugs on cardiac conduction as well as the effects of seizures or status epilepticus on the myocardium are other enigmatic aspects of the relations between epilepsy and heart.     

Anesthetic implications of epilepsy, status epilepticus, and epilepsy surgery

Epilepsy is a clinical paroxysmal disorder of recurring seizures, excluding alcohol or drug withdrawal seizures or such recurring exogenous events as repeated insulin-induced hypoglycemia. Epilepsy has a profound impact on each individual diagnosed with this disease. Seizures have been and are thought to arise as a result of abnormalities in (a) neural circuits, (b) excitation/inhibition balance, (c) potassium, and (d) genetic abnormalities. Therapy for epilepsy is either medical, entailing the use of a variety of antiepileptic drugs, or surgical. An urgent approach to seizure control is indicated when status epilepticus occurs. When all standard therapy fails, general anesthesia can be used to control status epilepticus. Surgery is an option in the treatment of epilepsy and requires extensive preoperative evaluation. The primary concerns for the neuroanesthesiologist anesthetizing the patient with epilepsy are the capacity of anesthetics to modulate or potentiate seizure activity and the interaction of anesthetic drugs with antiepileptic drugs. Proconvulsant and anticonvulsant properties have been reported for nearly every anesthetic. If seizure spikes are to be evoked during seizure surgery, then light anesthesia with a proconvulsant anesthetic is used. Conscious analgesia can be used for awake seizure surgery. However, if electrocorticography is not planned, then a general anticonvulsant anesthetic maintenance regimen is used. The latter technique also may be useful in patients whose anesthetic management is complicated by an incidental history of epilepsy.     

Behavioral and personality correlates of epilepsy: A review, methodological critique, and conceptual model.

Assesses the psychological risk associated with temporal lobe epilepsy and epilepsy in general and identifies other variables associated with an increased risk of psychopathology in epilepsy by reviewing 64 studies published since 1962. Methodological problems include the definition of epilepsy and the interictal state, sample selections, and the need for appropriate controls; until these problems are overcome, the behavioral ramifications of limbic system dysfunction in epilepsy will remain controversial. Greater methodological rigor in the field of epilepsy/psychopathology research will help assess whether animal studies of kindling of limbic structures with subsequent behavior changes have any validity for human psychopathology. There is a growing interest in the behavioral ramifications of neurological disease; however many factors outside of those that are biologically indigenous to the disorder play significant roles in the determination of psychopathology. A conceptual model (brain-, non-brain-, and treatment-related factors) is offered to help explain different proportions of variance for different behavior disorders. (6 p ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stabilization of active recombinant retroviruses in an amorphous dry state with trehalose

1. The objective of this investigation was to determine quantitatively whether experimental epilepsy is associated with a change in the pharmacodynamics of benzodiazepines in vivo. For that purpose the pharmacodynamics of midazolam were quantified by an integrated pharmacokinetic-pharmacodynamic approach in three different models of experimental epilepsy: amygdala kindling, cortical stimulation and genetic absence epilepsy. 2. The time course of the EEG effect was determined in conjunction with the decline of drug concentrations after intravenous administration of 10 mg kg(-1) midazolam. The pharmacokinetics of midazolam were most adequately described by a bi-exponential equation. No influence of epilepsy on the pharmacokinetics of midazolam was observed. 3. The increase in beta activity (11.5-30 Hz) of the EEG as derived by Fast Fourier Transformation analysis was used as pharmacodynamic endpoint. For each individual rat the increase in beta activity was directly related to the concentration in blood on the basis of the sigmoidal Emax pharmacodynamic model. In all three models a significant reduction in the maximal effect was observed, in amygdala kindling 28%, in the cortical stimulation model 49% and in genetic absence epilepsy 37%. No differences in the other pharmacodynamic parameters, E0 EC50,u and Hill factor, were observed. 4. It is inferred that in three different models of epilepsy there is a similar change in GABAergic functioning which is associated with a significant reduction in the intrinsic activity of midazolam in vivo. These models provide therefore a useful basis for further studies on the mechanism of epilepsy-induced changes in pharmacodynamics of anti-epileptic drugs.     

A genetic propensity to high factor VII is not associated with the risk of myocardial infarction in men

Interictal brain SPECT is useful for the localization of a seizure focus. Concomitant hypoperfusion of the ipsilateral thalamus on interictal SPECT has been noted for temporal lobe epilepsy. In this study, we aimed to evaluate the prevalence of thalamic hypoperfusion ipsilateral to temporal hypoperfusion (ipsilateral thalamic hypoperfusion) and to assess the usefulness of this finding for the lateralization of epileptic foci on interictal SPECT for temporal lobe epilepsy patients. METHODS: Forty-six patients with refractory temporal lobe epilepsy underwent interictal brain SPECT after intravenous injection of 555-740 MBq of 99mTc-ECD. Perfusion impairments in the brain, especially the temporal lobe and thalamus, were evaluated. The localization of seizure foci was determined in conjunction with scalp, ictal and cortical electroencephalography, MRI and clinical outcomes. Ictal SPECT was performed for 5 of the 12 patients. RESULTS: Concomitant decreased perfusion in both the temporal lobe and the ipsilateral thalamus was observed for 12 (26%) of 46 temporal lobe epilepsy patients on interictal brain SPECT. Seven patients showed hypoperfusion in the left temporal lobe and ipsilateral thalamus. Five patients showed hypoperfusion in the right temporal lobe and ipsilateral thalamus. In addition, hypoperfusion in the ipsilateral basal ganglia (ten patients) or contralateral cerebellum (four patients) was observed. CONCLUSION: Ipsilateral thalamic hypoperfusion is not uncommon in temporal lobe epilepsy. The exact mechanism causing ipsilateral thalamic hypoperfusion is uncertain; however, corticothalamic diaschisis may be an important factor. This finding may aid in the lateralization of seizure foci on interictal brain SPECT.     

Epilepsy diagnosis and localization in patients with antecedent childhood febrile convulsions

PURPOSE: A history of febrile convulsions (FC) is often obtained in patients presenting for surgical treatment of temporal lobe epilepsy (TLE), but it is not clear that preferential temporal localization of epilepsy is associated with antecedent FC. METHODS: We prospectively inquired about FC and their characteristics in all patients presenting to an epilepsy clinic through a patient questionnaire and interview. We studied the incidence of antecedent childhood febrile convulsions in relation to epilepsy diagnosis. RESULTS: FC were reported by 133 of 1005 study patients (13.2%). TLE was more likely to be preceded by FC (78/310, 25.2%) than extratemporal epilepsy (ETE) (12/216, 5.6%) (p < 0.000001) or generalized epilepsy (GE) (16/146, 11.0%) (p < 0.001). Patients with GE were more likely than patients with TLE to have had simple FC (p < 0.00005). Prolonged duration was the most common FC complex feature in TLE patients. CONCLUSIONS: We demonstrated a preferential association of FC with temporal lobe foci and a weaker association between FC and GE. FC does not appear to be a clear risk factor for ETE.     

New antiepileptic drugs. Overcoming the limitations of traditional therapy

Several new antiepileptic drugs have become available recently. Since seizures and epilepsy are common, primary care physicians are likely to encounter a patient who is taking one of these new medications. Successful medical management of epilepsy requires a proper understanding of medication half-life, indications, and side effects. Felbamate has a broad spectrum of efficacy but is limited by side effects and idiosyncratic reactions. Fosphenytoin has the efficacy of phenytoin and offers the advantage of intramuscular and intravenous dosing without the significant adverse effects associated with intravenous phenytoin; however, it is expensive. Gabapentin has minimal side effects and drug interactions yet has limited efficacy for seizures. Lamotrigine has broad seizure efficacy but requires a slow adjustment to therapeutic levels. Topiramate has minimal drug interactions, but therapy must be initiated slowly to avoid side effects. All of the new antiepileptics hold great promise in the management of patients with recurrent seizures.     

Prevalence of neurocysticercosis in individuals affected by epilepsy

INTRODUCTION: In this investigations, was carried out a neurocysticercosis (NC) prevalence study during seven months in the Instituto Neurológico de Antioquia with the purpose of known neurocysticercosis frequency as cause of epilepsy in patients older than ten years that we attended in our institute. MATERIAL AND METHODS: Computerized tomographies (CT) were made to 503 patients, with epilepsy, 24.7% of them were CT positive for NC. Cysticercosis enzyme linked immunoelectrotransfer blot (EITB) and enzyme linked immunoabsorbent assay (ELISA) test were made to 178 patients, 19.6% were EITB positive for NC and 5% ELISA positive for NC. Results. From this result it is possible to infer that about 8% of the 503 patients with epilepsy had cysticercosis, according to EITB that is the golden assay for NC. The CT and ELISA test had 94.3% and 27.7% sensitivity, respectively, according to EITB. The specificity of the CT for NC was 49.2% and specificity for ELISA test was 100% as compared to EITB. The multivariate analysis with logistic regression allowed to establish association of positive EITB with factors such as male sex, eating pork, headaches and multiple lesions in CT. CONCLUSIONS: Prevention and education actions are necessary for the interruption of the neurocysticercosis transmission chain in order to diminish the high prevalence of epilepsy in the country and its complication and consequences.     

Complexities of primary generalized epilepsy

Abnormal arousal responses paired with paroxysmal discharges and photosensitivity are the principal mechanisms in the precipitation of seizures in primary generalized epilepsy. The abnormal arousal responses show a consistent maximum over the frontal midline region. An exception from this rule was found in two children with primary generalized epilepsy (petit mal absences, one also with grand mal) with a strongly positive family history. In these patients, the generalized-synchronous bursts showed a maximum over the vertex (Cz electrode). Both of these children also had single spikes over the Rolandic region. A relationship between primary generalized and benign Rolandic epilepsy is demonstrated. Both forms of seizure disorder are based on dysfunction (hyperexcitability) rather than on a structural epileptogenic lesion. A dichotomy of dysfunctional and structural epilepsies is presented but gray zones of overlap indubitably exist. The limitations of the dichotomy concept are pointed out.