Seizure Provocation Research Articles

Gabapentin in childhood epilepsy: a prospective evaluation of efficacy and safety

Purpose: To evaluate the efficacy and safety of gabapentin (GBP) in partial epilepsy in children. Methods: We performed a prospective open label add-on study in 52 children and adolescents (age 1.8–17.5 years, mean 11.1 years) with refractory partial seizures. Gabapentin was added to one other baseline drug and the efficacy was rated according to seizure type and frequency. Results: The GBP dose ranged from 26 to 78 mg/kg per day (mean 52 mg/kg per day) and was well tolerated in most patients. The seizure frequency remained unchanged in 34 patients (65%). We saw a provocation of seizures in three children (6%). Initially 15 patients (29%) benefited from GBP: five (10%) with a seizure reduction of 50–74%, seven (13%) with a reduction of 75–99% and three (6%) became seizure free. All but three experienced a development of tolerance within the next weeks to months. Conclusions: Although gabapentin seems also to be safe in children, the efficacy in refractory partial seizures was disappointing.

Closed eyes during a seizure indicate psychogenic etiology: A study with suggestive seizure provocation

Psychogenic seizures are often difficult to distinguish from epileptic seizures. A saline infusion test with suggestion is a useful tool for diagnosis because psychogenic seizures can be elicited in about three-fourths of patients. We analyzed 100 psychogenic seizures provoked by suggestion in patients with and without a history of epileptic seizures. Most patients showed bilateral movements of the limbs, including head movements and pelvic thrust, mimicking generalized seizures. Ninety percent of patients had closed eyes, an uncommon feature during an epileptic generalized seizure; 10% of patients had open eyes. These patients frequently had a history of epileptic seizures. Suggestive provocation proved a safe and reliable diagnostic tool.

Aspartame and Seizure Susceptibility: Results of a Clinical Study in Reportedly Sensitive Individuals

The high intensity sweetener aspartame has been implicated anecdotally in seizure provocation. This possibility was investigated with a randomized, double-blind, placebo-controlled, cross-over study. After an extensive search, 18 individuals (16 adults and 2 children) who had seizures allegedly related to aspartame consumption were admitted to adult or pediatric epilepsy monitoring units where their EEG was monitored continuously for 5 days. Aspartame (50 mg/kg) or identically enpackaged placebo was administered in divided doses at 0800, 1000, and 1200 h on study days 2 and 4. All meals were uniformly standardized on treatment days. No clinical seizures or other adverse experiences were observed after aspartame ingestion. Mean plasma phenylalanine (Phe) concentrations increased significantly after aspartame ingestion (83.6 microM) as compared with placebo (52.3 microM). Results suggest that aspartame, in acute dosage of approximately 50 mg/kg, is no more likely than placebo to cause seizures in individuals who reported that their seizures were provoked by aspartame consumption.

Video game induced seizures.

Fifteen patients who experienced epileptic seizures while playing video games are described together with a review of 20 cases in the English literature. Nine of the 15 cases and all but two of the reported cases experienced their first seizure while playing video games. Two thirds of patients had idiopathic generalised epilepsy and mainly reported generalised tonic clonic seizures, but some had typical absence seizures and myoclonic jerks while playing video games. In this series, 30% with idiopathic generalised epilepsy had juvenile myoclonic epilepsy. Overall, 70% of patients with idiopathic generalised epilepsy were photosensitive to intermittent photic stimulation and the mechanism of seizure provocation was probably similar to that of television induced seizures, although sensitivity to specific patterns was sometimes important. Two children had self induced video game seizures. Non-photic factors such as excitement, fatigue, sleep deprivation, cognitive processing, and diurnal variation in susceptibility seemed to be important seizure precipitants, particularly in non-photo-sensitive patients. Twenty nine per cent of patients had partial (mainly occipital) video game associated seizures. Occipital spikes were common in the EEG of these patients. Photosensitivity to intermittent photic stimulation may have been important in two patients but in the others, who all played arcade video games, other mechanisms need to be considered. Video game associated seizures are a feature of several epileptic syndromes and differ in precipitants and appropriate management.

Provocation of nonepileptic seizures by suggestion in a general seizure population.

Nonepileptic seizures (NES) are common and are often diagnosed at epilepsy centers by video-EEG recording of both spontaneous and suggestion-induced episodes, but no study has evaluated provocative testing in a general seizure population. We studied consecutive patients with a tentative diagnosis of epilepsy using saline provocation during video-EEG recording, suggesting that this could produce a typical seizure. Of 52 patients, 40% had no response, 23% had responses unlike their seizures, and 37% had typical episodes (positive test). Patients whose usual episodes resembled complex partial seizures (CPS) were more likely to have NES than were patients with a history of generalized tonic-clonic seizures (GTC). Of patients with positive provocations, the primary physician predicted NES in 68% of cases. This preliminary study suggests that NES are frequent in a general neurology setting, and that saline provocation is a sensitive method of identifying NES.

Investigation of the opioid system in absence seizures with positron emission tomography.

The neuroanatomical and pathophysiological basis of primary generalised absences is uncertain. Administration of endogenous opioids has been shown to result in absence-like seizures in animal models. Positron emission tomography scans were performed in eight patients with primary generalised epilepsy and eight control subjects. Regional cerebral blood flow was measured interictally with C15O2, after which a 90 minute dynamic study with the opioid-receptor ligand 11C-diprenorphine was performed. Serial absences were precipitated by hyperventilation for 10 minutes, starting 30-40 minutes after injection of diprenorphine. Absences, with generalised spike-wave discharges on the EEG, occurred for between 10% and 51% of the provocation period. No individual (normal or patient) had any interictal focal abnormalities of cerebral blood flow. After provocation of serial absence seizures, there was increased diprenorphine elimination from the association cortex, but not from the thalamus, basal ganglia, or cerebellum, compared with control subjects and patients scanned without provocation of absences. It was possible to simulate the observed increased diprenorphine elimination following seizures in cerebral cortex using a two tissue compartment model, with an estimated 15-41% decrease in the specific tracer uptake rate constant (k3). These results suggest that endogenous opioids are released in the association cortex at the time of serial absences, lead to increased receptor occupancy, and may have an important role in the pathophysiology of generalised absences.

Preliminary Assessment of the Efficacy of Org 6370 in Photosensitive Epileptic Patients: Paradoxical Enhancement of Photosensitivity and Provocation of Myoclonic Seizures

Photosensitivity has proved to be a useful model to study the acute effects of experimental antiepileptic drugs (AEDs). The photosensitivity range is usually diminished or even abolished after administration of a known or experimental AED. An increase in photosensitivity, an unexpected reaction, was found in four photosensitive epileptic patients after oral ingestion of 500, 100, or 50 mg of Org 6370. Moreover, the three patients receiving doses of 100 and 500 mg reported nausea, dizziness, restlessness, and an increase in spontaneous epileptic seizures (myoclonus and in one patient a generalized tonic-clonic convulsion). The side effects coincided with peak Org 6370 serum levels. Our findings indicate that in the photosensitivity model experimental drugs with proven anticonvulsant properties in animals may increase rather than decrease the degree of patient photosensitivity. Photosensitive patients may represent a special subgroup of epileptic patients and therefore need to be classified as such.

Startle-induced seizures and their relationship to epilepsy: Three case reports

Three cases of startle-induced seizures are presented. Well-established concepts of classification of startle-induced seizures (“reflex epilepsy,” “startle epilepsy,” “startle disease/hyperexplexia”) are reviewed. Difficulty in classifying the presented cases is pointed out. In two patients, seizures could be provoked during video/EEG monitoring. In both cases, there were no epileptiform discharges during the seizures, suggesting startle disease. Nevertheless, one of the patients had a history of generalized tonic-clonic seizures; in the other, generalized seizures developed after slow withdrawal of medication, indicating startle epilepsy. The third patient, by history, had reflex epilepsy. Unfortunately, provocation of seizures under controlled conditions was not possible, rendering further classification of seizures into subtypes impossible.

Suppression of amygdala kindling with short interstimulus intervals: Effect of norepinephrine depletion

The rate of development of generalized kindled convulsions was profoundly influenced by the interval between amygdala stimulations. With stimulation every 10 min, nearly complete interference with the progression of kindling was observed in most rats, and hourly stimulation precipitated kindling rates three times longer than did once per day. Depletion of norepinephrine (NE), as a result of intracerebroventricular pretreatment with 6-hydroxydopamine, virtually eliminated the interference with kindling development seen in the vehicle control rats. Such depletion of NE, however, had little influence on the generalized responses once developed. At this stage, interference with seizure provocation was observed as truncated electroencephalographic seizures which were usually devoid of motor correlates. This interference was more profound in the shorter interstimulus intervals and was independent of NE depletion. Finally, when changing from the short kindling intervals of 10 min and 1 h to the longer interval of 24 h, an unexpected interference with seizure provocation was observed. The implication of these results for the biochemical basis of kindling and kindling as a model of learning are discussed.

Pharmacotherapy of epilepsy--current problems and controversies

Current trends and controversies in the antiepileptic drug therapy are reviewed from a clinical view. The usefulness of prophylactic therapy of febrile seizures and posttraumatic seizures or posttraumatic epilepsy is compromised by difficulties in the management of the patients especially by noncompliance. Previously untreated epilepsies can be treated successfully in 70--80% of the patients. Phenytoin or carbamazepine are equally effective for generalized tonic-clonic seizures of focal seizures, while absence seizures are controlled by ethosuximide or valproic acid. Only when the epilepsy is uncontrolled despite high plasma concentrations which cannot be raised because of side effects, a second drug should be given. A second drug is successful in about one out of six patients with focal epilepsy. Phenytoin, carbamazepine, phenobarbital and primidone seem to be equally effective for these drug-resistant cases. Status epilepticus can be treated with intravenous diazepam or phenytoin and, if necessary, with an infusion of phenytoin. Rectal diazepam is useful for acute pediatric therapy. Drugs of second choice are clonazepam, phenobarbital, lidocaine, and clomethiazole. In the pregnant epileptic patient a drop in the plasma concentration of antiepileptic drugs mainly through non-compliance and seizure provocation through sleep deprivation are major sources for the deterioration of epilepsies during pregnancy. The "fetal antiepileptic drug syndrome", malformations and an increased risk for epilepsy in the child are discussed as an interaction of parental epilepsy and drug-exposure during pregnancy. Finally, the interpretation of abnormal clinical chemistry data is reviewed. Disorders of the liver, bone, thyroid gland and blood are rarely seen in treated epileptic patients usually when specific risk factors are present. The over-interpretation of laboratory abnormalities e.g. an isolated increase of gamma-GT may lead to iatrogenic deterioration of epilepsy when the effective dose of the drug is reduced for unfounded fear of hepatic toxicity.