Seizure-free Period Research Articles

Factores pronósticos asociados al control médico en pacientes con evidencia radiológica de esclerosis mesial temporal

Patients with mesial temporal lobe sclerosis (MTS) usually have suffered a brain insult during early childhood, a febrile convulsion in most cases. Complex partial seizures start after a seizure free period of variable duration. These complex partial seizures have an stereotypic semiology. Often, these seizure are not controlled with medical therapy, previous studies shows a rate of control not superior of 30%. AIM. To know the prognosis for medical control of patients with MTS and to find related factors. The clinical characteristics of 51 patients with temporal lobe epilepsy and radiologic evidence of MTS (hippocampus atrophy or increased signal on T2 or Flair magnetic resonance sequences). 51 patients, of them 17 (34%) were men. 17 (34%) presented right MTS, 30 (60%) left MTS and 2 (4.3%) bilateral MTS. 16 patients (34.8%) referred autonomic aura, 14 (27.5%) psychic aura, 4 (7.8%) dysphasia and 13 (25.5%) no aura, in 2 (3.9%) aura were mixed: autonomic psychic. The aura was associated to the lesion laterality (p= 0.023) and to the reference of some antecedent of cerebral aggression during early childhood (p= 0.011). Concerning to the seizure control, 15 patients (29.2%) were seizure free in the last 6 month and 36 (70.6%) remaining uncontrolled. The associated factors to the medical control were the age of onset (p= 0.024) and the duration of the epilepsy (p= 0.018). Around 29% of patients with MTS can be controlled with medical therapy. Seizure control is related with later age of onset and short duration of the epilepsy

Risk factors for recurrence of epilepsy and withdrawal of antiepileptic therapy: a practical approach

In epileptic patients, treated with anticonvulsant drugs (AEDs), the question when and how an attempt should be made to withdraw therapy is a crucial point in the management of these patients. In recent years, many studies have identified the main risk factors for seizure recurrence after discontinuation of AEDs. Patients are more likely to have recurrences if there is a definite symptomatic aetiology, two or more different types of seizures, an abnormal neurological examination and a seizure onset at adolescence or later. In contrast, abnormal EEG has not been proved as a risk factor for recurrence. Moreover, the classification of epilepsy syndromes is another important predictor of the outcome for these patients. In practice, most authors suggest that medication is discontinued after a seizure-free period of two years. In this review we analyse data from the literature and we suggest a practical approach for safe anticonvulsant withdrawal, although the decision should always be made individually, weighing risks and benefits.

Serum s-100 protein is not a suitable seizure marker in temporal lobe epilepsy.

S-100 protein is a sensitive marker of various brain diseases; however, its role in epilepsy is controversially discussed in the literature. We therefore studied the temporal profile of serial concentrations of S-100 protein in serum after secondarily generalized tonic-clonic seizures during video-EEG monitoring. Ten patients with mesial temporal lobe epilepsy were prospectively studied. Serum S-100 protein was measured after a seizure-free period of > or =24 h (baseline) and 30 min, 3, 6, 12, and 24 h after a secondarily generalized tonic-clonic seizure of temporal lobe origin in nine and a convulsive status epilepticus in one patient. All S-100 levels were within the normal range, except for those of one patient at baseline. Mean values were 0.045 microg/L (range, 0.003-0.13 microg/L) at baseline, 0.038 microg/L (range, 0.003-0.09 microg/L) at 30 min, 0.036 microg/L (range, 0.003-0.08 microg/L) at 3 h, 0.034 microg/L (range, 0.003-0.07 microg/L) at 6 h, 0.034 microg/L (range, 0.003-0.08 microg/L) at 12 h, and 0.035 microg/L (range, 0.003-0.09 microg/L) at 24 h after seizure offset. There were no significant differences between mean concentrations at any interval postictally. We could not detect any significant alterations in serum S-100 protein concentration either after a single secondarily generalized tonic-clonic seizure or after convulsive status epilepticus in patients with temporal lobe epilepsy. Our data do not confirm previous work, which suggested serum S-100 protein to be a suitable marker for epileptic seizures.

Remisión a largo plazo de la epilepsia en la infancia: estudio prospectivo

To study the chance of achieving a long term remission of epilepsy in children.90 children aged under 14 years newly diagnosed of epilepsy were started on anticonvulsant treatment and prospectively followed. Initial remission was defined as a seizure free period with or without subsequent recurrences, terminal remission as a seizure free period without subsequent recurrences and terminal remission off treatment as terminal remission plus medication discontinued.The Kaplan Meier estimate of the probability of achieving a 3 year initial remission was 80% and 90%, of the probability of achieving a 5 year terminal remission was 59% and 68% and of the probability of achieving a 5 year terminal remission off treatment was 53% and 61% at 5 and 7 years, respectively. Univariate and multivariate analyses using the Cox proportionate hazards model revealed there was a greater probability of achieving a 3 year terminal remission off treatment for patients with idiopathic/cryptogenic etiology and for those who did not have recurrences during the first six months of treatment. Syndromic diagnosis at six months after initiating antiepileptic treatment was also useful for predicting the probability of remission.Over half of the epileptic children achieve a prolonged remission off treatment. The main prognostic factors are etiology, recurrence of seizures during the first six months and syndromic diagnosis.

Discontinuing antiepileptic drugs in patients who are seizure free on monotherapy

Objectives: To assess the recurrence rate of epilepsy attributable to discontinuation of treatment in seizure free patients and to identify the risk factors for recurrence. Methods: 330 patients referred to...

Individual state driving restrictions for people with epilepsy in the US.

States in the United States vary widely in their approaches to restricting driving for patients with epilepsy. Many states have shortened seizure-free restrictions or have adopted flexible regulations that consider individual clinical factors in determining driving privileges. The authors summarized state driving restrictions for patients with seizures, particularly unpublished regulatory practices, and determined the role and liability of physicians in judging driving safety for patients with epilepsy. The authors surveyed motor vehicle administration bureaus in the 50 states and the District of Columbia and compared the laws, regulations, and practices restricting driving for people with epilepsy. Key responses from a questionnaire were confirmed by state motor vehicle administrations with phone interviews and by a signed executive summary. Twenty-eight states, including the District of Columbia, have laws requiring patients with epilepsy to be free of seizures for single fixed periods, with a median restriction of six months (range, 3 to 12 months). Twenty-three states have adopted more flexible approaches to restricting driving, such as varying seizure-free restrictions based on individual clinical factors. Many states allow patients to drive after shorter seizure-free periods than stated in their laws. These practices, however, are usually unpublished and not easily accessible. Physicians helped determine when their patients may drive in 13 states and were not legally shielded for their assessments in six of these states. States vary widely in how they regulate driving for patients with seizures. These varied regulatory approaches present potentially valuable models to determine how driving might be best regulated to protect public and patient safety optimally while permitting patients with controlled seizures to drive.

Juvenile Myoclonic Epilepsy - an experience from north western India

The clinical data on cases of Juvenile Myoclonic Epilepsy (JME) were analysed. Response to initial small dosages (lower than usual) of sodium valproate and further lower maintenance dosages in patients who were seizure free for 2 years on drug were assessed. Seventy-six patients who were diagnosed to have Juvenile Myoclonic Epilepsy on definite criteria were studied. All patients were put on sodium valproate in dosages (lower than usual) for initial control and further lower maintenance dosage and response evaluated. The clinical profile was found to be similar as in other parts of India. There was a female preponderance and average delay of 4.9 years in final diagnosis. Forty-eight (63.1%) patients showed good control on 15 mg/kg/day dosages of sodium valproate. After a seizure free interval of 2 years, 58% of patients could be maintained on small dosages ranging from 3-5 mg/kg/day to 6-8 mg/kg/day. The majority of JME patients responded well not only to sodium valproate in dosages lower than usually prescribed but required very small dosages for maintenance after a seizure free period of 2 years.

Seizure Recurrence in Children With Focal Seizures and Single Small Enhancing Computed Tomographic Lesions: Prognostic Factors on Long-Term Follow-up

Single small enhancing computed tomographic (CT) lesions are common in children with focal seizures. There is a paucity of information regarding their long-term outcome and prognostic factors for seizure recurrence. The objective of this work was to study the frequency of seizure recurrence in children with single small enhancing computed tomographic lesions and to identify prognostic factors, if any, for seizure recurrence. A prospective long-term follow-up was conducted at the Advanced Pediatric Center, Postgraduate Institute of Medical Education and Research, an urban tertiary care teaching hospital. Sixty-three children between 2 and 12 years of age with focal seizures for less than 3 months and single small enhancing computed tomographic lesions were enrolled in a randomized, double-blind, placebo-controlled trial of albendazole therapy and followed up for 4 years. On long-term follow-up, the albendazole and placebo groups were left with 29 and 28 children, respectively. After several months of seizure-free period, antiepileptic drug was tapered off. Children with relapse underwent magnetic resonance imaging examination. All children were followed up for at least 18 months after stopping of the antiepileptic drug. Seizure recurrence was seen in three children each in both groups, after a mean interval of 6.4 weeks after stopping the antiepileptic drug. Magnetic resonance imaging revealed persistent chronic granuloma in 2 and calcified granuloma in 4 children. Residual lesions were significantly correlated with seizure recurrence. In children whose lesions completely disappeared, no seizure recurrence was seen even during shorter periods of antiepileptic drug treatment. Seizure recurrence was seen in a small number of children with focal seizures and single small enhancing computed tomographic lesions. It appears to be related to either a persistent or a calcified lesion.

Anticonvulsant effects of gamma surgery in a model of chronic spontaneous limbic epilepsy in rats

The management of intractable epilepsy remains a challenge, despite advances in its surgical and nonsurgical treatment. The identification of low-risk, low-cost therapeutic strategies that lead to improved outcome is therefore an important ongoing goal of basic and clinical research. Single-dose focal ionizing beam radiation delivered at necrosis-inducing and subnecrotic levels was investigated for its effects on seizure activity by using an established model of chronic recurrent spontaneous limbic seizures in rats. A single 90-minute period of repetitive electrical stimulation (inducing stimulus) of the hippocampus in rats elicited a single episode of status epilepticus, followed by a 2- to 4-week seizure-free period. Spontaneous recurrent seizures developed subsequently and persisted for the duration of monitoring (2-10 months). Simultaneous computerized electroencephalography and video recording were used to monitor the animals. After the establishment of spontaneous recurrent seizures, bilateral radiation centered in the ventral hippocampal formation was administered with the Leksell gamma knife, aided by a stereotactic device custom made for small animals. A center dose of 10, 20, or 40 Gy was administered using a 4-mm collimator. Control animals were subjected to the same seizure-inducing stimulus but underwent a sham treatment instead of gamma irradiation. In a second experiment, the authors examined the effects of gamma irradiation on the proclivity of hippocampal neurons to display epileptiform discharges. Naive animals were irradiated with a single 40-Gy dose, as already described. Slices of the hippocampus were prepared from animals killed between 1 and 178 days postirradiation. Sensitivity to penicillin-induced epileptiform spiking was examined in vitro in slices prepared from control and irradiated rat brains. In the first experiment, single doses of 20 or 40 Gy (but not 10 Gy) reduced substantially, and in some cases eliminated, behaviorally and electrographically recognized seizures. Significant reductions in both the frequency and duration of spontaneous seizures were observed during a follow-up period of up to 10 months postradiation. Histological examination of the targeted region did not reveal signs of necrosis. These findings indicate that single-dose focal ionizing beam irradiation at subnecrotic dosages reduces or eliminates repetitive spontaneous seizures in a rat model of temporal lobe epilepsy. In the second experiment, synaptically driven neuronal firing was shown to be intact in hippocampal neurons subjected to 40-Gy doses. However, the susceptibility to penicillin-induced epileptiform activity was reduced in the brain slices of animals receiving 40-Gy doses, compared with those from control rats that were not irradiated. The results provide rational support for the utility of subnecrotic gamma irradiation as a therapeutic strategy for treating epilepsy. These findings also provide evidence that a functional increase in the seizure threshold of hippocampal neurons contributes to the anticonvulsant influence of subnecrotic gamma irradiation.

Failed surgery for epilepsy. A study of persistence and recurrence of seizures following temporal resection.

From a series of 282 consecutive temporal resections for medically intractable epilepsy associated with mesial temporal sclerosis (MTS), dysembryoplastic neuroepithelial tumour (DNT) or non-specific pathology (NSP), 51 patients had persistent or recurrent seizures occurring at least monthly. Of these patients, 44 underwent detailed assessment of their postoperative seizures, which included clinical evaluation, interictal and ictal EEG and high-resolution MRI. Of the 20 patients with MTS in the original pathology, 14 (70%) had postoperative seizures arising in the hemisphere of the resection, the majority (12 patients) in the temporal region. Although MRI demonstrated residual hippocampus in five of these 12 patients, only one patient was considered to have seizures arising there, whilst the remainder had electroclinical evidence of seizure onset in the neocortex. In contrast, five of the MTS relapses (25%) had seizure onset exclusively in the contralateral temporal region. Among the 14 patients with non-specific pathology, relapse was also predominantly from the ipsilateral hemisphere (64%), but more relapsed from extratemporal sites compared with the MTS cases, including two with NSP who had occipital structural abnormalities. Although 70% of the 10 patients with DNT had postoperative partial seizures arising in the ipsilateral hemisphere, many (60%) had evidence of a more diffuse disorder with additional generalized seizures, cognitive and behavioural disturbance and multifocal and generalized EEG abnormalities. Nine patients (20%) had immediate postoperative seizure-free periods of at least 1 year, and seven of these had MTS in the operative specimen. Of these seven patients, four had ipsilateral temporal seizures and three had contralateral temporal seizures. Overall, few missed lesions were discovered on postoperative MRI and reoperations were performed or considered possible in a minority of cases. Despite well-defined preoperative electroclinical syndromes of temporal lobe epilepsy, many patients relapsed unexpectedly, either immediately or remotely from the time of surgery. Maturing epileptogenicity in a surgical scar was not, however, considered to be a significant primary mechanism in patients who relapsed after a seizure-free interval.

Psychiatric symptoms after therapy with new antiepileptic drugs: Psychopathological and seizure related variables

The purpose of this paper is to understand the association between antiepileptic drugs (AEDs), patient characteristics, changes in seizure pattern and emergent psychiatric disorder, i.e. psychosis or affective disorder. To this end we carried out a retrospective casenote study on 89 patients who developed psychiatric symptoms during treatment with topiramate, vigabatrin or tiagabine. The psychiatric problem was either an affective or a psychotic disorder (not including affective psychoses). It was discovered that 99% of the patients suffered from complex partial seizures with or without secondary generalization. More than half were on polytherapy with two or more other AEDs. Nearly two-thirds had a previous psychiatric history. There was a strong association between the type of previous psychiatric illness and the type of emerging psychiatric problem, both for psychoses and for affective disorders. Patients on vigabatrin had an earlier onset of epilepsy and more neurological abnormalities than those on topiramate. Those patients on lower doses had a shorter interval between the start of the AED therapy and the onset of the psychiatric problem. A seizure-free period was observed in more than half of the patients before they developed the psychiatric symptoms, and of these more were likely to develop a psychosis rather than an affective disorder. There seemed to be an association of suppression of right-sided seizures and the onset of the psychiatric problem. The conclusions drawn were that patients with a previous history of psychosis or affective disorder tended to develop the same psychiatric problem with new AEDs. Those with a seizure-free period before the onset of the psychiatric problem were more likely to develop a psychosis than an affective disorder.

Seizure recurrence after reduction of an antiepileptic drug in patients with unprovoked seizures and severe neurological abnormalities

A prospective study of antiepileptic drug (AED) reduction in patients with unprovoked seizures and severe neurological abnormalities after a seizure-free period of more than 5 years was performed. From a hospital for severely handicapped children (150 patients) and an institution for mentally handicapped people (89 persons), 13 patients were enrolled to this study after informed consent was obtained. All patients had experienced a seizure-free period of more than 7 years (median, 10 years). The patients had IQs of less than 50 and were almost dependent in their life. Five patients had additional motor deficits. The patients had been taking one to three AED (mean, 1.9) before reduction and only one AED was withdrawn. During the following 2years, four of the 13 patients (31%) showed a recurrence of seizures. The age at the time of the last seizure was lower in the seizure-free patients. As to the 10 patients with onset ages of 10 or less, a significant factor as to seizure recurrence was whether or not seizures were controlled before the age of 11 years (P < 0.05, Fisher's exact probability test). It is suggested that a patient with severe neurological abnormalities, in whom epilepsy or unprovoked seizures are controlled before the age of 11 years (i.e. before adolescence) could be a candidate for the reduction of AED.

Selective alterations of glycosaminoglycans synthesis and proteoglycan expression in rat cortex and hippocampus in pilocarpine-induced epilepsy

Proteoglycans and glycosaminoglycans are elements of matrix. In the nervous system, glycosaminoglycans modulate neurite outgrowth and are co-receptors for growth factors playing a crucial role in cell differentiation and synaptogenesis. The receptor of protein tyrosine phosphatase β (RPTPβ) is a chondroitin sulphate proteoglycan which plays an important role in neural morphogenesis and axon guidance mechanisms. Pilocarpine-treated rats present status epilepticus, which is followed by a seizure-free period (silent), by a period of spontaneous recurrent seizures (chronic), and the hippocampus of these animals exhibits cell loss and mossy fiber sprouting. Thus, the synthesis of heparan sulphate and chondroitin sulphate and the time course of RPTPβ immunoreactivity were studied in the hippocampus and cerebral cortex during these phases of pilocarpine-induced epilepsy. The results showed decreased synthesis of heparan sulphate during the acute phase and an increased synthesis of chondroitin sulphate during the silent period in the cortex and hippocampus. In control rats RPTPβ immunoreactivity was detected only in glial cells. After 6 h of status epilepticus the RPTPβ immunoreactivity was no longer detectable in the glial cells in both tissues and intense staining became evident in the matrix, surrounding CA3 and dentate gyrus and piriform cortex neurones. In the silent and chronic periods RPTPβ immunoreactivity was mainly detected in neuronal somata and fibers of neurones of hippocampus and cortex. These changes show a selective variation of synthesis and expression of glycosaminoglycans and RPTPβ in relation to epilepsy suggesting a molecular interplay between glia and neurones during seizures.

Relapse risk analysis after drug withdrawal in epileptic children with uncomplicated seizures

In an attempt to find the risk of relapse and factors predictive of risk of relapse, 97 children with epilepsy, withdrawn from their medication, followed in our outpatient clinic from 1990 to 1995 were included in this study. The overall relapse rate was 20.6%. All relapses occurred within 2 years after withdrawal started. Female gender, age at onset of seizures of more than 2 years, and the duration of withdrawal were found to be significant risk factors in relapse rate following univariate analysis. However, gender was not found to be significant in multivariate analysis. All other factors, including the duration of seizures prior to starting antiepileptic drug (AED) treatment, the number of seizure before the start of AED treatment, the period between AED induction and control of seizures, diagnostic yield from electroencephalogy (EEG) at diagnosis, the number of seizures after the onset of AED therapy, length of seizure-free period, aetiology of the seizures, a history of epilepsy in the immediate family, or previously experienced febrile convulsions were not significant factors in relapse rate. Significant risk factors for relapse rate also significantly affected relapse time. We conclude that when AED therapy is withdrawn from children with uncomplicated epilepsy, as in our patients, the two important risk factors, age at onset of seizures and the duration of withdrawal, can predict a poor prognosis with a higher relapse rate: this needs taking into consideration.

Growth-associated phosphoprotein expression is increased in the supragranular regions of the dentate gyrus following pilocarpine-induced seizures in rats

Neuroplasticity has been investigated considering the neuronal growth-associated phosphoprotein as a marker of neuronal adaptive capabilities. In the present work, studying the hippocampal reorganization observed in the epilepsy model induced by pilocarpine, we carried out quantitative western blotting associated with immunohistochemistry to determine the distribution of growth-associated phosphoprotein in the hippocampus of rats in acute, silent and chronic periods of this epilepsy model. The fibers and punctate elements from the inner molecular layer of the dentate gyrus were strongly immunostained in animals killed 5 h after status epilepticus, compared with the same region in control animals. Rats presenting partial seizures showed no alterations in the immunostaining pattern compared with saline-treated animals. The hippocampal dentate gyrus of animals during the seizure-free period and presenting spontaneous recurrent seizures was also characterized by strong growth-associated phosphoprotein immunostaining of fibers and punctate elements in the inner molecular layer, contrasting with the control group. As determined by western blotting analysis, growth-associated phosphoprotein levels increased following status epilepticus and remained elevated at the later time-points, both during the silent period and during the period of chronic recurring seizures. Pilocarpine-treated animals, which did not develop status epilepticus, showed no change in growth-associated phosphoprotein levels, indicating that status epilepticus is important to induce growth-associated phosphoprotein overexpression. The measurement of this overexpression could represent one of the early signals of hippocampal reorganization due to status epilepticus-induced damage.

Follow-up of psychogenic, non-epileptic seizures: a pilot study — experience in a Dutch special centre for epilepsy

A follow-up study was performed in 33 patients with proven (ictal EEG-CCTV) psychogenic, non-epilptic seizures (PNES). These patients received a questionnaire to evaluate seizures, treatment and rehabilitation. The response group consisted of 21 females (80% response) and seven males (100% response). Follow-up after diagnosis varied from 23–67 months. Seven patients (25%) reported that seizures had ceased and of the patients not seizure-free seven did report a seizure-free period after diagnosis of an average 6.7 months. Eight patients were on antiepileptic drugs again. Of 13 patients referred for psychotherapy, who also did receive treatment, six became free of seizures and seven did not. Of seven patients also referred, but who did not receive psychotherapy, all continued to have seizures. On a self-rating scale to compare “overall function" at the time of diagnosis and follow-up, 75% considered themselves to have “improved", but no improvement could be detected in psychosocial functioning.

Spatial and Temporal Relationships between C-Fos Expression and Kindling of Audiogenic Seizures in Wistar Rats

In a strain of Wistar rats selected in our laboratory, audiogenic seizures (AS), characterized by a wild running phase followed by a tonic seizure, can be elicited by exposure to sound. In these animals repeated daily stimulations induce permanent changes which reflect the extension of seizure activity from the brainstem to the forebrain. C-Fos immunoreactivity was used to further characterize the sound-susceptibility of the strain and to specify the spatiotemporal relationships between c-Fos expression and development of AS kindling. AS susceptible rats appeared to be more sensitive to a subthreshold sound as compared to controls. Sound-evoked wild running induced a similar pattern of c-Fos as a full AS in naive rats, confirming the epileptic nature of this early component. AS-induced c-Fos labeling in the auditory pathways of the brainstem extended to the forebrain with repetition of AS and marked increases in c-Fos expression sequentially occurred in the amygdala and perirhinal cortex, followed by the frontoparietal cortex, the piriform cortex, and finally the hippocampus and entorhinal cortex. These results show that the kindled AS preferentially propagate from the brainstem, through the amygdala and the perirhinal cortex, to the motor cortex, with the piriform cortex and hippocampus as secondary targets. No more c-Fos expression was detected 24 h after an AS. A down-regulation of cortical c-Fos induction was observed 1 and 2 days after daily exposure to kindled AS, with full recovery of c-Fos expression after a 5-day seizure-free period. This suggests a regulatory function of c-Fos expression in development of kindling.

Tyrosine phosphorylation is increased in the rat hippocampus during the status epilepticus induced by pilocarpine

Phosphorylation of tyrosine residue in proteins is an important modulatory process for membrane transduction and cell signaling and for several cellular functions. The concentration and distribution of phosphotyrosine proteins were analyzed in the hippocampi of rats in the model of epilepsy induced by pilocarpine using Western blotting and immunohistochemistry. The concentration of several phosphotyrosine proteins increased during status epilepticus . During the seizure-free period and the chronic period of this epilepsy model, the hippocampi of rats did not exhibit changes in the expression of these proteins. Immunohistochemistry showed an increased immunoreactivity throughout the hippocampal formation of rats 1 h after status epilepticus that was acutely induced by pilocarpine. Animals killed after 3 h of status epilepticus showed an increased expression of phosphotyrosine in the hippocampal hilus and CA3 regions. After 5 h of status epilepticus , phosphotyrosine immunoreactivity persisted only in the CA3 region. After 12 h of status epilepticus , the hippocampal formation exhibited a normal phosphotyrosine immunostaining, showing that the increased expression of these proteins is related to the acute phase and that several intracellular events could undergo modifications during the status epilepticus induced by pilocarpine.

Evaluating health-related quality of life outcomes in clinical trials of antiepileptic drug therapy.

To provide an overview of condition-specific health-related quality of life (HRQL) assessment in clinical trials of antiepileptic drug (AED) therapy in adults. We describe the key measurement issues in HRQL evaluation, identify the instruments that have been used in this population, summarize the psychometric characteristics of these instruments, propose areas of HRQL most likely to change with treatment, and offer recommendations for further research. We conducted a comprehensive review of the literature using repeated searches of the MEDLINE database together with a review of reference lists from published papers. Psychometric information on the instruments was gathered from published literature. Three epilepsy-specific HRQL measures were identified: the Epilepsy-Surgery Inventory (ESI-55), the Liverpool Assessment Battery, and the Quality of Life in Epilepsy Inventory (QOLIE, the 89-, 31-, and 10-item versions). One new measure, the Epilepsy Foundation of America (EFA) Concerns Index was also found. The psychometric characteristics of these instruments are discussed in relationship to performance or expected performance in a clinical trial setting. A review of descriptive studies and trials to date suggests that subscales reflecting the psychological and social domains of HRQL may be most sensitive to treatment designed to increase seizure-free periods, reduce seizure severity, and minimize undesirable side effects. Although evaluation of HRQL outcomes in clinical trials of epilepsy is still in its infancy, several reliable and valid condition-specific measures are available for understanding the impact of disease and treatment on HRQL. Further research is needed to determine minimal clinically important change scores and to assess the psychometric stability of measures across cultures and mode of administration (self, interview, telephone). Studies of patient preferences for health outcomes in the form of utilities will provide needed data for evaluating the cost-effectiveness of new treatments.

Ontogeny of altered synaptic function in a rat model of chronic temporal lobe epilepsy

In the limbic status model of chronic temporal lobe epilepsy, hippocampal stimulation induces acute status epilepticus in rats; recurrent, spontaneous seizures develop following an asymptomatic silent period lasting several weeks. Previous work has shown increased excitability and decreased inhibition in CA1 pyramidal neurons in chronically epileptic animals. To determine the relationship of altered cellular responses to seizure onset, in vitro intracellular recording was used to follow the evolution of changes in synaptic physiology occurring during the seizure-free silent period. Pyramidal cells displayed increasing epileptiform activity throughout the period investigated, 3–14 days following status; the mean number of evoked action potentials from 1.1±0.05 in control cells to 2.4±0.4 early (3 days after status) and 4.3±0.7 late (14 days) in the silent period. Monosynaptic inhibitory postsynaptic potentials mediated by γ-aminobutyric acid-A receptors in silent period cells differed markedly from controls. Area, rise time, and duration of these potentials decreased by 40–60% within 3 days following status and to values commensurate with chronically epileptic animals in 7 to 10 days. γ-Aminobutyric acid-B receptor-mediated IPSPs diminished more gradually in the silent period, reaching a minimum at day 14. In contrast, presynaptic γ-aminobutyric acid-B receptor function showed maximum impairment 3 days after status. The benzodiazepine type 1 receptor agonist zolpidem reduced hyperexcitability in both silent period and chronically epileptic cells, but was more effective at unmasking the underlying IPSP in silent period neurons. The results indicate that changes in different components of pyramidal cell inhibitory synaptic physiology associated with chronic epilepsy in this model evolve individually at different rates, but are all complete before seizure onset. Although the results do not imply causality, they do suggest that the development of physiological changes in CA1 pyramidal cells may contribute to the lag period preceding the onset of chronic seizures.