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PubMed2003

Assessment of the seizure susceptibility of Wistar Audiogenic rat to electroshock, pentyleneterazole and pilocarpine.

This work evaluates the seizure susceptibility of nai;ve female Wistar Audiogenic rats (WARs), a genetic model of reflex epilepsy in which seizures are induced by high-intensity sound stimulation (120 dB SPL), to other pro-convulsive stimuli: transauricular electroshock (ES), pentylenetetrazole (PTZ) and pilocarpine (PILO). Normal Wistar rats from the main breeding stock of the Institute of Biological Sciences, UFMG were taken as controls. Electroshock seizures were induced through a pair of ear-clip electrodes (10 mA, at a frequency of 60 Hz, applied for 1 s). In order to test WAR susceptibility to chemically induced seizures, animals were treated either with PTZ (37.5 mg/kg i.p.) or PILO (200, 270 and 300 mg/kg i.p.). Seizure severity was evaluated by appropriate behavioral severity index scales (SI) specific to each epilepsy model and tested for statistical significance using the non-parametric Mann-Whitney Rank Sum test. Results show a significantly greater susceptibility of WARs for ES (SI(WAR)=3+/-3/3, SI(Wistar)=1+/-1/1; median+/-interquartile range 25%/75%, P<0.01) and PTZ (SI(WAR)=4+/-4/4, SI(Wistar)=1+/-1/4; median+/-interquartile range 25%/75%, P<0.02), as indicated by significantly higher SI scores and shorter latencies for seizure onset (T(WAR)=71+/-7 s, T(Wistar)=94+/-8 s; P<0.05 Student t-test, mean+/-S.E.M.). Although PILO also caused higher SI scores in WARs (WAR(200 mg)=1+/-1/1, Wistar(200 mg)=1+/-1/1; WAR(270 mg)=1.5+/-1/2, Wistar(270 mg)=1+/-1/1.25; WAR(300 mg)=9+/-1/9, Wistar(300 mg)=4+/-1.5/7.5; median+/-interquartile range 25%/75%), statistically significant differences were not observed. In conclusion, our results show that WARs have an inherited broader predisposition for seizures.

Acoustic Stimulation↗

PubMed1999

Effects of adenosine receptor agonists and antagonists on audiogenic seizure-sensible DBA/2 mice.

We have studied the effects of selective and non-selective adenosine receptor agonists and antagonists in audiogenic-seizure-sensitive DBA/2 mice, an animal model of generalized reflex epilepsy. With the exception of the adenosine A3 receptor agonist, N6-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine (IB-MECA), all the agonists studied prevented the development of audiogenic seizures in a dose-dependent manner. The ED50 values against the clonic phase of the audiogenic seizures were low, that is: 0.06 mg/kg, i.p., for the adenosine A1 receptor agonist, 2-chloro-N6-cyclopentyladenosine (CCPA), 0.02 and 0.03 mg/kg, i.p., for the adenosine A2A receptor agonists, 2-(4-(2-carboxyethyl)-phenylamino)-5'-N-ethylcarboxamidoadenosine (CGS 21680) and 2-hexynyl-5'-N-ethyl-carboxamidoadenosine (2-HE-NECA), and 0.7 mg/kg, i.p., for the adenosine A1/A3 receptor agonist, N6-2-(4-aminophenyl)ethyladenosine (APNEA). Conversely, the non-selective agonist, N-ethyl-carboxamidoadenosine (NECA), was highly potent, the ED50 being 0.0005 mg/kg, i.p. In the absence of auditory stimulation, the adenosine receptor antagonists increased the incidence of both clonic and tonic seizures in DBA/2 mice. The ED50 values were: for caffeine, 207.5 mg/kg, i.p., for the adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), 327.8 mg/kg i.p., for the adenosine A2A receptor antagonists, 3,7-dimethyl-1-propylxanthine (DPMX), 86.7 mg/kg i.p., for the (E,18%-Z,82%)7-methyl-8-(3,4-dimethoxystyryl)-1,3-dipropylxanthine (KF 17837), 69.1 mg/kg i.p., and 5-amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo-(4,3-c)1,2,4-triazolo(1,5 -c)-pyrimidine (SCH 58261), 321.8 mg/kg i.p. The rank order of convulsant potency in our epileptic model, following intracerebroventricular administration, was DPCPX > DMPX > 1,3,7-trimethyl-8-(3-chlorostyryl)xanthine (CSC) > KF 17837 > Caffeine > SCH 58261 > 5-amino-9-chloro-2-(2-furyl)-1,2,4-triazolo(1,5-c)quinazoline (CGS 15943). Following a subconvulsant audiogenic stimulus of 83 dB, all adenosine receptor antagonists induced both tonic and clonic seizures. The ED50 values for such proconvulsant effects were: for caffeine 0.04 mg/kg, i.p., for the adenosine A receptor antagonist, DPCPX, 5.84 mg/kg, i.p., for the adenosine A2A receptor antagonists, DMPX, 0.02 mg/kg, i.p., CGS 15943, 0.29 mg/kg i.p., KF 17837, 0.57 mg/kg, i.p., CSC 0.12 mg/kg, i.p. and SCH 58261 0.07 mg/kg, i.p., respectively. These data suggest that stimulation of adenosine A1 and A2A receptors is involved in the suppression of seizures.

Animals↗

PubMed2001

Anti-epileptiform effects of audiogenic seizure priming on in vitro kindling in rat hippocampus.

The effect of priming for audiogenic seizures (AGS) on the development of epileptiform activity in the hippocampus was studied using in vitro kindling (IVK) in Long-Evans rats. AGS priming consists of intense auditory stimulation during a critical period of auditory development, resulting in sound-induced clonic convulsions upon subsequent testing. Between postnatal day (PND) 28 and 50, slices from subjects primed and sham-primed for AGS on PND 18 were used for recording responses in area CA1 of hippocampus following Schaffer collateral stimulation from stratum radiatum of area CA2/CA3. The developmental priming procedure, which enhances auditory brainstem excitability, resulted in fewer afterdischarges in slices from primed subjects across initial IVK stimulation sequences. These results suggest that changes in excitability that occur with acoustic priming can initially diminish selective epileptiform response characteristics in forebrain areas such as the hippocampus.

Acoustic Stimulation↗

PubMed1997

Felbamate and meprobamate: a comparison of their anticonvulsant properties.

The anticonvulsant effect of felbamate and meprobamate were compared in a series of models for seizure activity and regarding their neurotoxic action. In the MES test, felbamate was active below neurotoxic doses. Meprobamate had an ED50 in the range of neurotoxic doses. The s.c. PTZ test was influenced by meprobamate in a fairly low dosage (ED50 66 mg/kg), but for felbamate no clearly dose-related effect could be shown up to 150 mg/kg. Reflex epilepsy in gerbils was stronger suppressed by meprobamate (ED50 34 mg/kg) than by felbamate (ED50 63 mg/kg). In amygdala kindled rats, meprobamate proved to be the most active compound, both regarding treatment of fully kindled rats, development of kindling and independent discharges from a mirror focus (secondary epileptogenesis), which were fully suppressed by oral treatment with 80 mg/kg for 30 days. Both drugs were weakly effective in a model for absence epilepsy in rats. The unexpectedly high activity of meprobamate justifies a second look at the anticonvulsant properties of the drug, especially since it was extensively used as an anxiolytic drug in the past with few obvious serious side effects.

Animals↗

PubMed1997

Fos-immunoreactive responses in inferior colliculi of rats with experimental audiogenic seizure susceptibility.

Audiogenic seizure (AGS) susceptibility is a reflex epilepsy of rodents in which acoustic stimulation evokes wild running attacks and subsequent convulsions. Susceptibility can be induced in non-susceptible strains by treatments causing transient or permanent hearing losses as long as these occur during the neonatal period. The defect which is the basis of susceptibility has been proposed to be a failure of developmental organization of inferior colliculus (IC) into frequency selective zones. That is, high frequency stimuli evoke responses in broader arrays of neurons in ICs of susceptible rats than in those of neonatally untreated (non-susceptible) controls. Nonetheless, this observation has been made only in rats in which susceptibility was induced by exposure to intense noise on postnatal day (PND) 14. By contrast, the present study examines whether unusually broad topographic responses are also characteristic in ICs of rats made susceptible by the neonatal administration of low doses of the ototoxic antibiotic, kanamycin (KM). Patterns of Fos-like immunoreactivity (Foslir) induced by seizures or pure tone stimuli were compared in ICs of adult Wistar rats which neonatally had been (a) sham-treated; (b) noise-exposed on PND 14; or (c) injected on PNDs 9-12 with 100 mg/kg KM. It was found that sound-triggered seizures in the two experimental groups resulted in induction of Foslir primarily within cortical areas of IC. By contrast, pure tones evoked unusually broad responses in the central nucleus of ICs of both susceptible groups but not in those of controls. Additionally, in the KM-treated rats, the range of frequencies evoking abnormal responses extended one octave lower than was characteristic of noise-exposed rats. The earlier schedule of treatments in the KM model may account for this inasmuch as low frequency response domains undergo development at younger ages. The similarity of results in the two models suggests failure of development of frequency selective fields in IC is indeed the common basis of experimentally induced susceptibility to sound-triggered seizures.

Acoustic Stimulation↗

PubMed1999

A retarded boy with seizures precipitated by stepping into the bath water.

This report describes the unusual case of a boy with partial deletion in the proximal region of a long arm of chromosome 2 and reflex epilepsy. Seizures with identical onset were precipitated predictably by two independent triggers, micturition and immersion of the feet in tepid or hot water. A seizure precipitated by immersion could be reproduced under video and EEG monitoring. The EEG seizure onset was in the central midline region.

Child↗

PubMed2001

Tooth brushing-induced seizures: a case report.

We report a 28-year-old woman of normal intellect, who had three late-onset seizures with unusual ictal features and secondary generalization during prolonged and vigorous tooth brushing. Neurologic examination and brain magnetic resonance imaging (MRI) were normal, but interictal EEG showed left frontal epileptiform activity. Reasonable precautions (regular but briefer and less vigorous brushing of her teeth) combined with a moderate dose of carbamazepine effectively prevented seizure recurrence. This case may be an example of cryptogenic form of reflex epilepsy with seizures induced exclusively by tooth brushing.

Adult↗

PubMed2003

Tactile-evoked rolandic discharges: a benign finding?

PURPOSE: This retrospective study was undertaken to determine if patients having tactile-evoked rolandic discharges were a more "benign" patient population than those with spontaneously occurring nontactile rolandic discharges and to determine whether the presence of tactile-evoked rolandic discharges was a marker for the future development of epilepsy, as previously reported. METHODS: During this 8-year study, 304 patients were seen with rolandic discharges. These patients all had tactile stimulation of their hands and/or feet. They formed two groups: patients with spontaneous rolandic discharges that could not be evoked by tactile stimulation (NT) and patients with spontaneous rolandic discharges that could be enhanced with tactile stimulation (TE). Over a 14-month period, every patient had tactile stimulation of both hands and both feet, resulting in a third group of patients having rolandic discharges seen only with tapping (TO). RESULTS: Tactile-enhanced discharges constituted 38.2% of all rolandic discharges. Patients with TE and TO discharges had a higher incidence of normal development and intelligence, normal neurologic examinations, and a lower incidence of seizures and focal or generalized background abnormalities on their EEGs. Only one patient with normal background and no coexisting epileptiform abnormalities had partial motor seizures with corresponding contralateral central discharges. Only two patients who had no seizures at the time of their first EEG subsequently went on to develop seizures. Neither fit the pattern of the seizure disorder described in the literature. CONCLUSIONS: It is hypothesized that tactile-evoked rolandic discharges are a benign, age-related phenomenon, which do not represent a marker for the future development of epilepsy and are not the interictal electrographic correlate to an already existing seizure disorder.

Adolescent↗

PubMed2003

Effects of topiramate in two models of genetically determined generalized epilepsy, the GAERS and the Audiogenic Wistar AS.

PURPOSE: The antiepileptic effects of topiramate (TPM) were assessed in two models of genetically determined generalized epilepsy. The model of nonconvulsive epilepsy used was a model of absence seizures, the GAERS (Genetic Absence Epilepsy Rat from Strasbourg); and the model of convulsive seizures was an audiogenic rat model, the Wistar Audiogenic Sensitive (AS) rat. METHODS: GAERS were equipped with four cortical electrodes over the frontoparietal cortex, and the duration of spike-and-wave discharges (SWDs) on the EEG was recorded for periods of 20 to 120 or 300 min. In Wistar AS, the occurrence of, latency to, and duration of one or two wild running episodes and tonic seizures were recorded. RESULTS: In the 16 GAERS studied, TPM (10, 30, and 60 mg/kg) dose-dependently reduced the expression of SWD that almost totally disappeared at the two highest doses between 40 and 120 min. SWD duration returned to control levels by 180 and 280 min after the injection of 30 and 60 mg/kg TPM, respectively. In Wistar AS, 10 mg/kg TPM induced the occurrence of a second running episode not present in control rats, indicative of a decrease in sensitivity of the rats to the stimulus and increased by 330% the latency to the tonic seizure that still occurred in the eight rats studied. At 30 and 60 mg/kg, the latency to wild running increased by 140%; the second running episode was suppressed in six and seven rats, respectively, whereas the tonic seizure occurred only in one of the eight rats studied at these two doses. CONCLUSIONS: These results support the broad spectrum of antiepileptic activity of TPM, confirming its efficacy in primary generalized seizures of both tonic-clonic and of the absence type.

Animals↗

PubMed2000

The relationship between photosensitive temporal lobe epilepsy and eye closure activity.

We describe a 16-year-old female patient affected by photo-induced temporal lobe epilepsy. During intermittent photic stimulation she showed a photoparoxysmal response in the EEG. This case was diagnosed from clinical symptoms, single photon emission computer tomography, and EEG data. The clinical symptoms were relieved by the administration of carbamazepine. As these photoparoxysmal responses were observed not only during photic stimulation, but also when patient was closing her eyes during an eye-opening test in complete darkness, we propose the existence of an alternative pathway such as from the extraocular muscles or orbicularis oculi, or activation of cortical activity due to the change of consciousness by closing eyes in inducing photosensitive epilepsy. We describe an additional case and discuss a novel aspect of photo-induced temporal lobe epilepsy.

Adolescent↗

PubMed2003

Effects of bilobalide on cerebral amino acid neurotransmission.

Bilobalide is one of many active constituents found in EGb 761 (definition see editorial), which is extracted from Ginkgo biloba leaves. Whilst there is good, sound evidence that bilobalide exhibits neuroprotective actions in a variety of model systems, there is currently no consensus on its mechanism of action. This present communication summarises the results we have obtained with this compound on excitatory amino acid neurotransmission in the central nervous system using both neurochemical and electrophysiological techniques. Bilobalide was shown to reduce glutamate and aspartate release elicited by both high potassium-containing artificial cerebrospinal fluid (aCSF) or veratridine from mouse cortical slices. In addition, bilobalide had a very potent effect (IC (50) 2.7 microM) on glutamate release elicited by hypoxia/hypoglycaemia-induced release from rat cortical slices. Electrophysiologically, bilobalide also decreased the frequency of gamma-aminobutyric acid (GABA) uptake inhibitor-induced depolarisations in mouse cortical slices, an effect probably mediated by a decrease in glutamate release. No definitive conclusions can be reached concerning the mechanism of action of bilobalide, but an ability to decrease excitotoxic amino acid release, particularly glutamate, would suggest that this is a probable mechanism to account for its neuroprotective properties.

Animals↗

PubMed2005

Typical absence seizures triggered by photosensitivity.

PURPOSE: To describe the characteristics of patients with typical absence seizures (TASs), consistently triggered by photosensitivity. METHODS: Consecutive patients having TAS induced by intermittent photic stimulation were included in the study. All clinical parameters, EEG, and video-EEG data were assessed during the long-term follow-up. Statistical analyses were performed with SPSS 10.0 software. RESULTS: Nine female and two male patients with a mean age at onset of 14 +/- 5.9 years (range, 7-27 years) and with a mean follow-up of 9 +/- 7.56 years had photosensitive TASs. They constituted 7.64% of absence epilepsies and 0.4% of all patients seen in our tertiary center. The seizures were usually subtle and had a reported frequency of 1 to 9 times daily. Seven patients were clinically photosensitive and reported that some of their TASs were induced by photic stimuli in daily life. All patients also had spontaneous TASs, and four of them had generalized tonic-clonic seizures. EEG results did not show any distinctive features when compared with those of other cases with TASs. Remission could not be achieved in five patients with antiepileptic drug treatments, and we always observed relapses after drug discontinuation or dose reduction in the remaining six cases in remission. Spontaneous remission did not occur even in the five patients older than 30 years. CONCLUSIONS: TASs triggered by photosensitivity are a rare and heterogeneous clinical condition with a marked female preponderance. It is notable that TASs do not remit in these cases.

Adolescent↗

PubMed1979

Ictal body scheme disturbance induced by looking through a small opening.

The case of a patient is reported in which seizures consisting of a feeling that the left arm was absent were induced by looking through a small opening (e.g. camera view finder). The EEG showed right parietal sharp wave discharges between and during such seizures. This observation is interpreted as an example of a reflex epilepsy triggered by the specific stimulus of looking through a small opening, and involving the right parietal lobe.

Adolescent↗

PubMedDate not supplied

Unusual form of seizures induced by eye closure.

Seizures induced by eye closure are a rare but well-recognized form of reflex epilepsy. Two types have been reported: those induced by movement of the eyelids and those caused by lack of visual input. The EEG pattern is typically that of spike and wave discharges, either isolated to the occipital regions or greatest there. We report the case of a 19-year-old woman with a previously undescribed form of seizures induced by eye closure in whom both the physical act of eye closure and total lack of visual input were required for induction of a seizure. Both the EEG pattern of paroxysmal high-amplitude generalized beta activity and poor response to medication were different from what has been previously noted in patients with seizures induced by eye closure. We believe that a third form of seizures induced by eye closure exists and that its prognosis may be significantly worse than that of previously reported forms.

Adult↗

PubMed1999

Interictal spikes increase cerebral glucose metabolism and blood flow: a PET study.

PURPOSE: In patients with reflex epilepsy, it is sometimes possible to evoke interictal spikes predictably, thus providing an uncommon but important experimental paradigm for examining the physiological changes produced by epileptiform discharges. METHODS: To examine the changes in regional cerebral blood flow (rCBF) and glucose consumption (rCMRglc) produced by interictal spikes, we performed positron emission tomography (PET) scans with the blood-flow tracer [15O]H20 and with [18F]fluorodeoxyglucose in a patient with fixation-off epilepsy. The scans were performed in states of high and low spike frequency produced by eye closure and opening, respectively. RESULTS: The rCBF study revealed a focal increase in blood flow associated with the state of increased interictal spiking. The focus was in the posterior portion of the left superior parietal lobule (Talairach coordinates: x: -36, y: -71, z: 39; t = 4.5; p<0.05) and corresponded to the site of maximal ictal EEG abnormality recorded with implanted electrodes. In a volume of interest of 10-mm diameter centered on the t statistic peak in the rCBF study, the mean rCMRglc was 39.1 micromol/100 g/min with eyes open and 44.1 micromol/100 g/min (13% increase) with eyes closed. An identical activation paradigm was used in six normal subjects studied with functional magnetic resonance imaging. In the normal subjects, no significant activation was observed in the parieto-occipital region, indicating that the changes observed in the patient were due to interictal spiking rather than to task performance alone. CONCLUSIONS: Interictal spiking produces focal increases in cerebral blood flow and glucose metabolism.

Adult↗

PubMed2005

Speech-induced aphasic seizures in epilepsy caused by LGI1 mutation.

PURPOSE: Patients with autosomal dominant lateral temporal lobe epilepsy (ADTLE) may have seizures precipitated by sound or speech. We have examined a patient with speech-induced seizures caused by an LGI1 mutation (C46R). METHODS: A clinical study and a video-EEG recording using interrogative speech as the activation procedure was performed in a 23-year-old man. RESULTS: He had experienced short episodes of sensory aphasia in situations in which he was suddenly verbally addressed. Voices became distorted, and he could not comprehend despite hearing words. The day after a late party, his girlfriend unexpectedly spoke to him. Her speech became unintelligible to him. He did not reply and had a generalized tonic-clonic (GTC) seizure. During an EEG, he was suddenly asked for the names of his siblings. He answered, but lost understanding of the further conversation and described how syllables floated together with an echoing character. With a versive movement to the right, another GTC occurred. In the EEG, rhythmic 6-Hz activity built up in the frontotemporal areas starting on the left side with bilateral and posterior spreading. Postictal slowing was symmetrical, and no aphasia was noted on awakening. CONCLUSIONS: To our knowledge, this is the first video-EEG recorded seizure in LGI1-caused ADTLE. This peculiar seizure semiology and precipitating effect of speech may serve as a marker for identifying further individuals with this particular phenotype and genotype and may indicate that the LGI1 gene may have a physiologic function connected to the human capacity for speech and language.

Acoustic Stimulation↗

PubMed2006

Musicogenic seizures can arise from multiple temporal lobe foci: intracranial EEG analyses of three patients.

PURPOSE: To determine the ictal-onset zone of musicogenic seizures by using intracranial EEG monitoring. METHODS: Musicogenic seizures in three patients with medically intractable musicogenic epilepsy were first localized by using noninvasive methods including, in one patient, ictal magnetoencephalography (MEG) and magnetic resonance spectroscopy (MRS). The ictal-onset zones in these patients were then further localized using by intracranial EEG monitoring, and the outcomes of the two patients who underwent epilepsy surgery were determined. RESULTS: Patient 1's musicogenic seizures localized to the right lateral temporal lobe, patient 2's originated in the right mesial temporal lobe, and patient 3's arose independently from both mesial temporal lobes. Patients 1 and 2 underwent resective epilepsy surgery and are seizure free (Engel class I). CONCLUSIONS: Musicogenic epilepsy is a heterogeneous syndrome with seizures that can arise from multiple temporal lobe foci. Patients with medically intractable musicogenic epilepsy and with unilateral ictal onset zones may be considered candidates for resective epilepsy surgery.

Adult↗

PubMed2006

Role of valproate across the ages. Treatment of epilepsy in children.

In June 2005 a team of experts participated in a workshop with the objective of reaching agreement on the place of valproate use in the treatment of paediatric epilepsy patients. A general "consensus of the meeting" was that the initiation of antiepileptic drug (AED) treatment should be based on a seizure-syndromic approach in children. Participants of the meeting also agreed that valproate is currently the AED with the broadest spectrum across all types of seizures and syndromes. Its superiority has been shown over almost 40 years of clinical experience. The best results are seen in idiopathic generalized epilepsy with or without photosensitivity, idiopathic focal and symptomatic generalized tonic-clonic seizures (GTCS). Evidence supports the use of valproate, ethosuximide and lamotrigine in absence epilepsies and the use of carbamazepine, lamotrigine, oxcarbazepine, phenytoin, topiramate, valproate and phenobarbital for primary GTCS. For new AEDs trials have been undertaken to define their therapeutic role but studies comparing their role to 'old' broad-spectrum drugs in specific syndromes are missing. Experts concluded that intravenous (i.v.) valproate is a useful agent in the treatment of non-convulsive status epilepticus (SE). There is an easy transition to oral treatment following i.v. valproate use. The discussion also concluded that, despite the lack of studies, valproate is an interesting, underutilized alternative in convulsive SE but more controlled studies are needed. The side effects of valproate use are well documented. Its effect on cognition and behaviour is more favourable than many of the other AEDs which is an important consideration in children. Overall, the clinical consensus of the meeting was that valproate's well established therapeutic properties far outweigh the negative side effects. Contraindication or withdrawal should be assessed individually.

Anticonvulsants↗