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Prognosis for total control of complex partial and secondarily generalized tonic clonic seizures. Department of Veterans Affairs Epilepsy Cooperative Studies No. 118 and No. 264 Group.

BACKGROUND: Two prospective observations of adults with symptomatic, localization-related (partial) epilepsy included 1,102 patients in VA multicenter studies (VA-118 and VA-264). Analyses assessed the likelihood of remaining seizure free for 12 and 24 months after initiating adequate antiepileptic drug therapy. METHODS: Patients were grouped as having only secondarily generalized tonic-clonic seizures (GTC), only complex partial seizures (CPS), or both types (MIXED) at entry. The cumulative proportion of patients remaining seizure free with standard antiepileptic drug therapy was determined by actuarial life table methods. RESULTS: At 12 months, 70% and 61% of GTC patients (VA-118 and VA-264, respectively) had no further GTC; 53% and 50% of MIXED, predominantly GTC patients had no further GTC, 21% and 28% of CPS patients had no further CPS and 98% and 91% were seizure free for GTC; 32% and 35% of MIXED, predominantly CPS patients had no further CPS, and 62% and 51% of patients with MIXED seizure types remained seizure free for CPS for 12 months after enrollment. CONCLUSIONS: The overall prognosis for control of seizures of any type for 12 months was best for those who had only GTC at entry (55% and 48%), worst for those who had only CPS at entry (23% and 26%), and intermediate for those with MIXED seizures at entry (32% and 25%) (all p < 0.0001). Prognosis can be based on the predominant seizure type in patients with multiple types.

Adult↗

Geriatric epilepsy: a review.

After the turn of the century, the proportion of population over 60 years of age is expected to be over 20%. Recent epidemiologic studies show a higher incidence of new-onset epilepsy in the population over 60 years of age compared with preceding decades of life. The predominant seizure type in up to 80% of these new cases of epilepsy is simple and complex partial manifestation. This paper reviews the literature documenting the increased incidence of partial seizures in the aging population, explores the known etiologies of new-onset epilepsy, and uses five case vignettes presenting with complex partial symptomatology.

Aged↗

Ring chromosome 20 mosaicism in a girl with complex partial seizures.

The authors report an 11-year-old girl with epilepsy, poor school-performance and minor behavioural disorders. The epilepsy is characterized by complex partial seizures, sometimes progressing secondarily into generalized tonic-clonic seizures, and is poorly controlled by medical treatment. Chromosomal analysis revealed a ring chromosome 20 mosaicism. The affected patient shows signs of ring chromosome 20 syndrome, characterized in the present case by poor school-performance, behavioural disorders and epilepsy.

Child↗

Nonconvulsive status epilepticus in adults and children.

Nonconvulsive status epilepticus (SE) accounts for approximately one-quarter of all cases of SE. The actual proportion may be higher because patients with nonconvulsive SE may go unidentified. This disorder may be divided into generalized (absence) or partial (complex partial) forms. Nonconvulsive SE may occur de novo or in patients with epilepsy. Absence SE is considered more frequent and is characterized by a continuous neurocognitive alteration. Complex partial SE may be associated with recurrent seizure activity and a cycling of the clinical states. Treatment includes antiepileptic drug(s) (AEDs) and avoidance of seizure precipitants. Electrophysiological studies are necessary to confirm the diagnosis of nonconvulsive SE and to monitor the response to AED therapy. Prompt recognition and treatment may be necessary to avoid neurological morbidity in select patients. Epilepsy with continuous spikes and waves during slow sleep (ESES) and the Landau-Kleffner syndrome are two rare childhood disorders that are difficult to classify but may be appropriate to include in a discussion of nonconvulsive SE.

Adult↗

Sleep deprivation does not affect seizure frequency during inpatient video-EEG monitoring.

OBJECTIVE: To determine whether acute sleep deprivation facilitates seizures during inpatient monitoring in a controlled protocol. METHODS: Eighty-four patients with medically refractory partial epilepsy undergoing inpatient monitoring were assigned in consecutive blocks to either sleep deprivation every other night or to normal sleep. In both groups, subjects were requested to stay awake during the day, from 6 AM to 10 PM. In the sleep deprivation group, patients also stayed awake between 10 PM and 6 AM every other night beginning with Day 2. Patients were removed from sleep deprivation if they had two or more secondarily generalized seizures within 24 hours. Patients were removed from the normal sleep group and were sleep deprived if they did not have a complex partial or secondarily generalized seizure by Day 6 of monitoring. In these patients removed from sleep deprivation or from normal sleep, data were analyzed up to and including the day of removal from the protocol. RESULTS: The sleep deprivation and normal sleep subjects did not differ in age, sex, seizure localization, or percent dosage reduction in antiepileptic drugs from baseline at days 1 to 3 of monitoring. Protocol duration was 6.5 +/- 2.4 days (mean +/- SD) for the sleep deprivation group and 5.8 +/- 2.0 days for the normal sleep group. Seizures per day for complex partial, secondarily generalized, and combined complex partial and secondarily generalized, calculated from admission until end of protocol, did not differ significantly between the two groups. CONCLUSION: Acute sleep deprivation did not affect seizure frequency during inpatient monitoring in our patients with intractable complex partial seizures with secondary generalization.

Adult↗

Univariate genetic analyses of epilepsy and seizures in a population-based twin study: the Virginia Twin Registry.

The purpose of this study was to examine the roles of genetic and environmental factors in the etiology of epilepsy and seizures in twins ascertained from the Virginia Twin Registry. Health history information on twins was collected by questionnaire. Concordance rates were calculated and used to estimate degree of concordance for seizure types in monozygotic (MZ) and dizygotic (DZ) twin pairs. Univariate twin analyses were performed for each epilepsy and seizure type to determine models which best explained observed variation. Health history information concerning epilepsy and febrile seizure occurrences was provided by members of 8,655 twin pairs; 6,684 of these supplied additional information reporting absence, complex partial, tonic-clonic, and unspecified seizures. Models including additive genetic and unique environmental factors best explained febrile seizures, epilepsy, complex partial seizures, and unspecified seizures. For complex partial seizures, however, the contributions of genetic and environmental effects did not vary across gender. These results show that, under univariate analysis methods, genetic factors played an important role in the expression of seizures in epilepsy, febrile seizures, unspecified seizures, and complex partial seizures. Additional support for these findings was provided by the concordance results for all categories except male twins reporting complex partial seizure occurrence. However, environmental influences still remained an important factor in seizure expression in these specific categories.

Adolescent↗

Status epilepticus in idiopathic generalized epilepsy.

Status epilepticus (SE) can take various forms in idiopathic generalized epilepsy (IGE), some of which forms also occur in symptomatic or focal epilepsies. Although the clinical semiology of the SE episodes may be similar in these different epilepsies, the frequency, response to treatment and prognosis differ. (a) Convulsive SE is surprisingly uncommon in IGE and much less common than in the secondarily generalized or partial epilepsies. Also, when it does occur, it usually responds rapidly to treatment. (b) Typical absence SE occurs only in patients with IGE (the subcategories with typical absence seizures) and also in the syndrome of de novo absence SE of late onset. This form of nonconvulsive SE should be differentiated from atypical absence SE, which occurs in the secondarily generalized epilepsy encephalopathies, and from complex partial SE which occurs in focal epilepsy. The clinical symptoms of these three types overlap but the prognosis and response to treatment are different. The mechanisms underlying absence SE are uncertain and may include both genetic and environmental factors. The termination of absence seizures has been hypothesized to be due to persistent activation of a depolarizing current in thalamocortical neurons that inactivates T-type calcium channels. SE could thus result from dysfunction of this channel or mechanisms that hyperpolarize thalamocortical neurons-these include decreased cortical inhibition, increased reticular thalamic neuronal activity or increased thalamocortical neuron GABA(B)-receptor activation. (c) Generalized electrographic SE is encountered in IGE in the syndrome of phantom absence with GTCS. It also occurs in ESES and in the Landau-Kleffner syndrome. The seizure phenomenology overlaps with the focal SE of temporal or frontal lobe epilepsy. (d) Myoclonic SE is also uncommon in IGE but occurs in juvenile myoclonic epilepsy. It is more commonly encountered in progressive myoclonic epilepsies, myoclonic-astatic epilepsy and in the Dravet syndrome. (e) Autonomic status occurs largely in the Panayiotopoulos syndrome. It is included here under the rubric of IGE, although the epilepsy has focal as well as generalized features and its nosological position is controversial. Fifty percent of seizures in this syndrome could be classified as status epilepticus. There is no doubt that convulsive SE can result in cerebral damage. In animal models of focal SE, nonconvulsive forms can also result in cerebral damage, but cerebral damage is not observed in animal models of absence SE. Similarly, cerebral damage seems not to occur in the forms of nonconvulsive SE in human IGE.

Animals↗

If a first antiepileptic drug fails to control a child's epilepsy, what are the chances of success with the next drug?

OBJECTIVE: This study was carried out to determine how often a child's epilepsy is controlled and remits if a first antiepileptic drug (AED) fails to control seizures. STUDY DESIGN: We used the Nova Scotia population-based epilepsy study, which identified children between 1977 and 1985 who had two or more unprovoked seizures without progressive cause and followed them up for at least 4 years. Seizure types were partial, primary, and secondarily generalized (excluding absence seizures). The study documented success or failure of the initial AED in the first year of treatment, as well as long-term seizure control and remission. RESULTS: The number of eligible children was 417, with an average follow-up period of 8 years. The initial prescribed AEDs were phenobarbital (48%), carbamazepine (38%), and phenytoin (11%). Overall, 345 (83%) children received only one AED in the first year of treatment; 61% became free of seizures and no longer required AED treatment at the end of follow-up (remission). Only 4% of those treated with a single AED during the first year later experienced intractable epilepsy. In contrast, 72 of 417 (17%) had inadequate seizure control with their first AED and received a second AED, with only 42% having complete remission of their epilepsy. The 72 children in whom seizures were not controlled with the first AED were more likely to have neurologic deficits (p = 0.01) and complex partial seizures (p = 0.01), and 29% had intractable epilepsy (p < 0.0001). CONCLUSIONS: If the first AED is not efficacious, the outcome is less favorable, although many children will have remission of their epilepsy. Invasive or complex treatments for epilepsy with partial and generalized tonic-clonic seizures should not be used until at least two AEDs have failed to control seizures.

Age of Onset↗

An expert system for the diagnosis of epilepsy: results of a clinical trial.

BACKGROUND: Artificial intelligence is an area where computer systems are used to solve real-life problems that require expert human intelligence. Expert systems serve as an effective alternative to supplement the dearth of human experts in a narrow domain of applications. We developed an expert system named SEIZ using DIAGNOS (an expert system shell for diagnostic applications) for the diagnosis and management of epilepsy. METHODS: A clinical trial was done to test the reliability of SEIZ. The clinical and demographic data from the medical records of 50 patients with epilepsy who attended an epilepsy clinic were provided to the expert system. The system-generated diagnosis was compared with the clinical diagnosis. RESULTS: The seizure types and epileptic syndromes for the 50 patients included generalized -tonic-clonic seizure (14), absence (4), complex partial seizure (18), simple partial seizure (4), juvenile myoclonic epilepsy (5) and other epileptic syndromes (3). There were two cases of hysterical conversion reaction. There was concordance in the diagnosis between the expert system and clinician in 47 cases (94%). The overall sensitivity was 94% and the specificity was 100% for absence, generalized tonic-clonic seizures, simple partial seizures and juvenile myoclonic epilepsy; 94% for complex partial seizures and 98% for hysterical conversion reaction. CONCLUSION: This expert system could generate reliable diagnoses for patients with epilepsy. Such a system may be useful for a doctor in a remote or peripheral area where an expert on epilepsy is not available.

Adult↗

[Infantile partial seizures due to temporal lesions--analysis of 4 cases].

We studied 4 cases of complex partial seizures due to temporal lesions presenting with benign partial epilepsy in infancy. None of them had neurologic abnormalities. All cases had complex partial seizures, and two had lateralizing signs. All cases had temporal lesions. One of them was detected only by fluid-attenuated inversion recovery (FLAIR) imaging. Histopathologically they were astrocytomas (grade 2 and 3), glio neuronal hamartoma and focal cortical dysplasia. The present cases suggest that patient with infantile complex partial seizures should be carefully followed up, even after the disappearance of seizures, by serial MRI examination including FLAIR imaging and by clinical observation.

Astrocytoma↗

[Temporal lobe epilepsy: effect of focus side on the autonomic regulation of heart rate?].

Epileptic activity can modulate reactions of the autonomic nervous system. Although there is some evidence of a differential left/right hemispheric influence on the cardiovascular system, diverse investigations have shown controversial results. In our study, complex partial seizures of patients with temporal lobe epilepsy were recorded using subdural electrodes, thus providing reliable information on the focus side. We analyzed the preictal and ictal heart rates of 27 patients, 16 revealing right and 11 revealing left temporal foci. During the seizures, both groups showed a significant increase in heart rate. Preictal tachycardia was only significant in the right focus group, whereas no significant change in heart rates could be detected in the left focus group. Our results confirm a right hemispheric lateralization of sympathetic cardiac control.

Adult↗

Relationship of seizure frequency to hippocampus volume and metabolism in temporal lobe epilepsy.

PURPOSE: To examine the relationship between frequency of complex partial (CPS) and secondarily generalized tonic-clonic seizures (sGTCS) on hippocampal volume (HV) and temporal lobe metabolism. METHODS: We performed volumetric magnetic resonance imaging (MRI) and positron emission tomography with 18fluorodeoxyglucose (18FDG-PET) in 32 patients with epilepsy. Temporal lobe foci were localized by ictal video-EEG. RESULTS: We did not find any association between CPS frequency or lifetime number of sGTCS and HV or metabolism ipsilateral to electroencephalographic focus. CONCLUSION: The progress of metabolic or pathologic abnormalities of temporal lobe epilepsy may not be altered by adequate seizure control. The presence of an epileptic focus might be associated with progressive neuronal injury even in clinically well-controlled patients.

Adult↗

Kindling as a model of drug-resistant partial epilepsy: selection of phenytoin-resistant and nonresistant rats.

Complex partial seizures comprise the major uncontrolled seizure type in adult patients with epilepsy. Any improvement of our understanding of the mechanisms through which these seizures are often refractory to antiepileptic drugs is therefore of considerable importance. By examining the effects of the anti-epileptic drug phenytoin in a large group of kindled rats, a widely used model of complex partial seizures, animals with different sensitivity to this drug were selected. Using determination of the focal seizure threshold for evaluation of phenytoin's anticonvulsant effect, most animals (about 60%) showed variable effects in response to phenytoin. However, about 20% of the animals ("phenytoin nonresponders") showed no increase in their focal seizure threshold at repeated test trials with phenytoin, and 20% ("phenytoin responders") exhibited reproducible increases in focal seizure threshold after injection of phenytoin. Phenytoin responders and nonresponders thus selected were used for subsequent experiments. The different response of focal seizures to phenytoin was not related to differences in pharmacokinetics or location of the stimulating electrode. Although phenytoin reproducibly increased the threshold for induction of afterdischarges in responders, it did not alter severity or duration of the elicited seizure response. In contrast to phenytoin, carbamazepine induced increases in focal seizure threshold in all kindled rats. Duration of seizures and afterdischarges were significantly reduced by carbamazepine in phenytoin responders, but not in nonresponders, although plasma levels of carbamazepine were the same in both groups. The difference in response of kindled rats to phenytoin was restricted to kindled seizures, because phenytoin induced the same anticonvulsant effect on the threshold for generalized tonic electroconvulsions (determined via transauricular electrodes) in both groups of kindled rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Temporal lobectomy that spares the amygdala for temporal lobe epilepsy.

Rationale, surgical techniques, and results in 70 patients with complex partial seizures who underwent temporal lobectomy with sparing of the amygdala are discussed. Removal of entorhinal cortex may be the common denominator that explains the similar results obtained with different types of temporal lobectomies for epilepsy.

Adolescent↗

The influence of seizure type on the efficacy of plasma concentrations of phenytoin, phenobarbital, and carbamazepine.

Plasma concentrations of phenytoin, phenobarbital, or carbamazepine were monitored prospectively during successful single-drug therapy in 78 patients who had various types of epileptic seizures. Mean plasma concentrations necessary for complete control of tonic-clonic seizures alone were as follows: phenytoin, 14 micrograms/mL (n = 28); phenobarbital, 18 micrograms/mL (n = 10); and carbamazepine, 5.5 micrograms/mL (n = 2). Epilepsy with simple or complex partial seizures alone or together with tonic-clonic seizures was completely controlled at the following plasma concentrations: phenytoin, 23 micrograms/mL (n = 25); phenobarbital, 37 micrograms/mL (n = 5); and carbamazepine, 7 micrograms/mL (n = 7). Higher plasma concentrations of phenytoin, phenobarbital, and carbamazepine are necessary for control in epilepsy with simple or complex partial seizures compared with epilepsy with tonic-clonic seizures alone. The efficacy of plasma concentrations of phenytoin, phenobarbital, and carbamazepine varies with the type of seizure.

Adult↗

Complex partial and secondarily generalized seizure patients: cognitive functioning prior to treatment with antiepileptic medication. VA Epilepsy Cooperative Study 264 Group.

This investigation of cognitive functioning in patients with symptomatic localization-related (partial) epilepsy prior to administration of antiepileptic medication is part of a nationwide prospective, double-blind study of drug efficacy and longitudinal changes in cognition associated with seizure disorders. Recently-diagnosed patients with complex partial or secondarily generalized tonic clonic seizures, equated for age, education and IQ, were compared with normal controls on a battery of neuropsychological tests: verbal and figural memory measures (Rey auditory verbal learning test, Rey Osterrieth complex figure), and a brief behavioral toxicity battery comprising measures of motor function, concentration and mental flexibility (Lafayette grooved pegboard, controlled word association test, Stroop, paced auditory serial addition test [PASAT]). Control subjects perform significantly better than both groups of seizure patients on several measures of motor speed/integration and memory, specifically the pegboard and the RAVLT learning (3-5) and recall trials. Secondarily generalized seizure patients show greatest impairment. They perform significantly worse than patients with complex partial seizures and control subjects on the controlled word association test and the most demanding Stroop color word trial, both measures of concentration and mental flexibility. These findings document deficits in memory as well as concentration and motor function in complex partial and in secondarily generalized seizure patients prior to treatment with antiepileptic medication.

Adult↗

Nonconvulsive status epilepticus: Epilepsy Research Foundation workshop reports.

In April 2004, a group of physicians with an interest in nonconvulsive status epilepticus representing a spectrum of opinion met in Oxford, sponsored by the Epilepsy Research Foundation (a charitable organization), to discuss and debate the definition, diagnosis and treatment of nonconvulsive status epilepticus. We felt that such a meeting would be useful, as nonconvulsive status epilepticus is a subject that provokes strong reactions, perhaps largely due to the relative lack of evidence and the surfeit of opinion. The meeting was arranged such that there were formal talks followed by a discussion led by one of the attendees. We present here the extended abstracts of the main talks with the points raised by the discussants. Despite disagreements on certain issues there was much in the way of consensus. First, it was agreed that nonconvulsive status epilepticus is a term that covers a range of disparate conditions with varying prognoses and treatments. The agreed definition was thus suitably vague, A< >. Secondly, it was agreed that even within a specific condition (e.g. complex partial status epilepticus), the prognosis and treatment depends upon the context in which the condition occurs (e.g. in the critically ill, in coma, in the A< > and in people with prior epilepsy). Perhaps, most importantly it was agreed that we lacked good clinical data, and the challenge was to design good studies for a condition that is underrecognised and often difficult to diagnose.

Brain Damage, Chronic↗

Social communication in children with epilepsy.

BACKGROUND: This study examined measures of social communication that involve the use of language in formulating and organizing thoughts and its relationship with seizure-related, developmental, cognitive, and behavioral variables in 92 children with complex partial seizure disorder (CPS), 51 with primary generalized epilepsy (PGE), and 117 normal children, aged 5.1-16.9 years. METHODS: Coding the children's speech samples with the Kiddie Formal Thought Disorder Rating Scale (Caplan et al., 1989) and Halliday and Hasan's (1976) analysis of cohesion demonstrated social communication deficits in both seizure disorder groups. RESULTS: The CPS patients had both formal thought disorder and cohesion deficits and the PGE group had mild cohesion deficits. IQ, as well as fronto-temporal and bilateral spike and wave activity were associated with the severity of the social communication deficits of the CPS group. The social communication deficits of the PGE group, however, were related to IQ and seizure control. CONCLUSIONS: Recurrent CPS and PGE and fronto-temporal localization of epileptic activity might impair the development of children's communication skills.

Adolescent↗