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PubMed2005

Symptoms of narcolepsy in children misinterpreted as epilepsy.

Differentiating an epileptic seizure from some other paroxysmal event is a common challenge in clinical practice. Many paroxysmal events mimic epileptic seizures and misdiagnosis can have disastrous consequences. Incorrectly identifying an event as an epileptic seizure can lead to unnecessary investigations and instigation of inappropriate treatment regimes. We report five patients referred to regional Paediatric Neuroscience Centres for investigation of events initially suspected of being epileptic seizures. All five patients were subsequently diagnosed as having narcolepsy. Suspected diagnoses were absence epilepsy (four patients), generalized epilepsy with astatic seizures (two patients) and focal epileptic seizures (two patients). Diagnostic confusion arose because lack of responsiveness due to excessive sleepiness was mistaken for epileptic absences, and cataplexy was confused with a variety of seizure types. In each case, videotape recording of clinical events aided in making the diagnosis of cataplexy. At presentation, all five children had excessive daytime sleepiness with cataplexy. Following correct diagnosis and appropriate management, an improvement in symptoms was reported in all cases. Narcolepsy/cataplexy should be included in the differential diagnoses of paroxysmal disorders, particularly if there are associated sleep symptoms or behavioural difficulties. It is important to take a sleep history when evaluating any disorder of the central nervous system.

Attention Deficit Disorder with Hyperactivity↗
PubMed1980

Flash-evoked afterdischarge in rat as a model of the absence seizure: dose-response studies with therapeutic drugs.

The flash-evoked afterdischarge (FEAD) is a self-sustained burst of wave-and-spike complexes recorded from occipital cortex in the rat and other animals in response to a single light flash. On the basis of behavioral experiments and studies employing single doses of antiepileptic drugs, FEAD has been proposed as a model of the absence seizure. In order to test the validity of FEAD as an absence seizure model, the present experiments determined dose-response relationships for the suppression of FEAD by six antiepileptic drugs with established clinical profiles. It was found that phenobarbital, ethosuximide, and trimethadione suppressed FEAD in a dose-related manner, and that ethosuximide was approximately three times as potent as trimethadione. Mephenytoin produced a maximal reduction of FEAD of only 30 to 40%, which was not dose-related. Neither phenytoin nor acetazolamide suppressed FEAD. The results obtained with ethosuximide, trimethadione, and phenytoin are qualitatively similar to their therapeutic effects in absence epilepsy. The FEAD model failed, however, to unequivocally predict the therapeutic efficacy of mephenytoin or acetazolamide. In this respect, it is similar to the metrazol seizure model. It is concluded that FEAD is a valid absence seizure model with a pharmacological predictive value that is at least as good as the metrazol model.

Acetazolamide↗
PubMed1999

Ion channels and the genetic contribution to epilepsy.

Recent application of genetic analysis to rare, hereditary epilepsies has resulted in the identification of mutations in genes encoding ion channels or functionally related proteins in several human and animal syndromes. Reviewed here are selected human and murine epilepsies that result from ion channel mutations. In humans, three autosomal-dominant disorders--benign familial neonatal convulsions, nocturnal frontal lobe epilepsy, and "generalized epilepsy with febrile seizures plus"--result from mutations affecting voltage-sensitive potassium channels, a central nicotinic acetylcholine receptor, and a voltage-sensitive sodium channel, respectively. In mice, four genetically distinct, autosomal-recessive models of absence epilepsy are caused by mutations in genes encoding three types of calcium channel subunits and a sodium-hydrogen ion exchanger. These findings suggest that variation in genes encoding ion channels could determine susceptibility to common human epilepsies.

Chromosome Aberrations↗
PubMed2000

Genome search for susceptibility loci of common idiopathic generalised epilepsies.

Genetic factors play a major role in the aetiology of idiopathic generalised epilepsies (IGEs). The present genome scan was designed to identify susceptibility loci that predispose to a spectrum of common IGE syndromes. Our collaborative study included 130 IGE-multiplex families ascertained through a proband with either an idiopathic absence epilepsy or juvenile myoclonic epilepsy, and one or more siblings affected by an IGE trait. In total, 413 microsatellite polymorphisms were genotyped in 617 family members. Non-parametric multipoint linkage analysis, using the GeneHunter program, provided significant evidence for a novel IGE susceptibility locus on chromosome 3q26 (Z(NPL) = 4.19 at D3S3725; P = 0.000017) and suggestive evidence for two IGE loci on chromosome 14q23 (Z(NPL) = 3.28 at D14S63; P = 0.000566), and chromosome 2q36 (Z(NPL) = 2.98 at D2S1371; P = 0.000535). The present linkage findings provide suggestive evidence that at least three genetic factors confer susceptibility to generalised seizures in a broad spectrum of IGE syndromes. The chromosomal segments identified harbour several genes involved in the regulation of neuronal ion influx which are plausible candidates for mutation screening.

Chromosomes, Human, Pair 14↗
PubMed1994

Juvenile myoclonic epilepsy.

BACKGROUND: Recognition of the significance of juvenile myoclonic epilepsy (JME) in the English-language neurological literature is relatively new. There are many factors responsible for delay in diagnosis of JME, including lack of familiarity with the syndrome, failure to elicit a history of myoclonic jerking and absence or generalized tonic-clonic seizures predating myoclonic jerks in some patients. METHODS: The medical and electroencephalographic (EEG) records of seven Chinese children with JME, four males and three females, were reviewed. RESULTS: The age of onset ranged from 10 to 14 years with mean 11.8 +/- 1.6 years. The precipitating factors were sleep deprivation (5/7), photostimulation (3/7), hyperventilation (2/7) and menstruation (1/3). Childhood and juvenile absence epilepsies predated JME in three and one patients, respectively. All patients had concomitant grand mal on awakening. Generalized 3-4 Hz polyspikes-wave complexes occurred in all patients, and two patients had additional 3-4 Hz spike-wave complexes. These activities were provoked with photic stimulation (3/7) and hyperventilation (2/7). All patients were treated with valproate for more than four years, and relapse occurred six months to one year after discontinuation of valproate. CONCLUSIONS: JME is a benign generalized epilepsy with a strong genetic basis. Valproate is the drug of choice up to now, but long-term (life-long) medication may be needed.

Adolescent↗
PubMedDate not supplied

[Electroencephalographic studies of family members of patients with juvenile myoclonic epilepsy].

Juvenile myoclonic epilepsy (JME) is a common idiopathic generalized epilepsy (IGE); it has a clinical and probably a strong genetic relation to the other IGE forms. Generalized spike/polyspike-wave discharges (SW/PSW) are typical of all IGEs. The aim of our study was to determine the incidence of epilepsy and SW/PSW in EEG of family members of 12 JME patients. 35 first degree relatives aged over 15 years were examined. 40 min EEG with 5 min HV were recorded. IGE was diagnosed in 3 (8.6%) persons: JME in 2 and childhood absence epilepsy (CAE) in 1 person. Six more relatives (17.1%) had typical SW/PSW traits in EEG. Thus the IGE features were found in 9 (25.7%) individuals--members of 7 out of 12 families (58%). EEG of 7 other relatives (20%) revealed non-specific episodic diffuse or focal abnormalities. The above results reveal higher incidence of different kinds of ICEs and typical EEG traits in families of JME patients. This findings confirm familial susceptibility to IGE and may be helpful in genetical counselling.

Adolescent↗
PubMed1996

Anticonvulsant drug effects on spontaneous thalamocortical rhythms in vitro: phenytoin, carbamazepine, and phenobarbital.

When perfused with a medium containing no added Mg2+, rodent thalamocortical brain slices generate spontaneous generalized thalamocortical discharges of several types. Two of these discharges, termed simple and complex thalamocortical burst complexes (sTBCs and cTBCs), are physiologically and pharmacologically similar to the spike-wave discharges of generalized absence epilepsy and to the discharges underlying generalized tonic-clonic seizures, respectively. In a further characterization of the pharmacology of generalized thalamocortical discharges recorded in rodent thalamocortical slices, the actions of anticonvulsants effective in control of partial and generalized tonic-clonic seizures, but not generalized absence seizures, were studied on these rhythms. The effects of phenytoin, carbamazepine, and phenobarbital were tested against sTBCs and cTBCs recorded in vitro in rodent thalamocortical slices. When applied in clinically relevant concentrations, phenytoin and carbamazepine were very effective in reducing or blocking cTBCs. These drugs were much less effective in controlling sTBCs. Phenobarbital was effective in controlling both sTBCs and cTBCs, but the level of block was greater for cTBCs. Therefore, it appears that sTBCs and cTBCs are quite distinct in their relative sensitivity to anticonvulsant drugs, and this differential sensitivity parallels the relative effectiveness of these drugs in controlling generalized absence and generalized tonic-clonic seizures.

Animals↗
PubMed2002

Altered kinetics and benzodiazepine sensitivity of a GABAA receptor subunit mutation [gamma 2(R43Q)] found in human epilepsy.

The gamma-aminobutyric acid type A (GABA(A)) receptor mediates fast inhibitory synaptic transmission in the CNS. Dysfunction of the GABA(A) receptor would be expected to cause neuronal hyperexcitability, a phenomenon linked with epileptogenesis. We have investigated the functional consequences of an arginine-to-glutamine mutation at position 43 within the GABA(A) gamma(2)-subunit found in a family with childhood absence epilepsy and febrile seizures. Rapid-application experiments performed on receptors expressed in HEK-293 cells demonstrated that the mutation slows GABA(A) receptor deactivation and increases the rate of desensitization, resulting in an accumulation of desensitized receptors during repeated, short applications. In Xenopus laevis oocytes, two-electrode voltage-clamp analysis of steady-state currents obtained from alpha(1)beta(2)gamma(2) or alpha(1)beta(2)gamma(2)(R43Q) receptors did not reveal any differences in GABA sensitivity. However, differences in the benzodiazepine pharmacology of mutant receptors were apparent. Mutant receptors expressed in oocytes displayed reduced sensitivity to diazepam and flunitrazepam but not the imidazopyridine zolpidem. These results provide evidence of impaired GABA(A) receptor function that could decrease the efficacy of transmission at inhibitory synapses, possibly generating a hyperexcitable neuronal state in thalamocortical networks of epileptic patients possessing the mutant subunit.

Amino Acid Substitution↗
PubMed2005

Epidemiology of idiopathic generalized epilepsies.

Idiopathic generalized epilepsies (IGEs) are a relatively new category of disorders defined by strict clinical and electroencephalogram (EEG) features proposed by the International League Against Epilepsy (ILAE) classification of epileptic syndromes. IGEs are usually easy to diagnose when clinical and EEG data are collected, but epilepsy is not synonymous with epileptic syndrome. So far, IGEs are studied in the large group of epilepsies of undetermined or unknown etiology although the genetic origin is now largely accepted. ILAE-proposed criteria are helpful in the clinical and therapeutic management of IGEs, but many epidemiologic studies still confuse the cryptogenic and idiopathic groups. Some syndromes in childhood, which are completely described by strict electroclinical criteria such as the absence epilepsies, juvenile myoclonic epilepsies, are usually included and analyzed in epidemiologic studies; however, other epileptic syndromes observed in infancy, such as benign familial neonatal seizures and benign myoclonic epilepsy in infancy, are quite rare and are usually excluded from epidemiologic surveys because they are difficult to describe completely in electro-clinical terms. Another strong limitation in the study of epidemiology of IGEs is the lack of EEG data, either because EEG is not available or the routine EEG is normal. This is particularly relevant in the inclusion of patients with only tonic-clonic seizures. IGEs encompass several different syndromes, and a few patients shift from one phenotype to another. The overlapping of some syndromes during infancy and adolescence increased the difficulty to individualize strictly the correct syndrome. Many discrepancies can be observed in the distribution of the different syndromes included in the group of IGEs, because the strict criteria for classifying these syndromes proposed by the ILAE are often not respected. With this understanding, the general frequency of IGEs can be assessed at 15-20% of all epilepsies. The frequency and the distribution of incidence and prevalence of the different syndromes are tentatively reported and discussed. When the term idiopathic is used following the restrictive ILAE criteria, the mortality data concerning patients with idiopathic epilepsies do not show an increased standardized mortality ratio.

Adult↗
PubMed2004

Nifedipine affects the anticonvulsant activity of topiramate in various animal models of epilepsy.

Topiramate (TPM), a new generation antiepileptic drug was investigated for its anticonvulsant effects in various models of genetically determined and chemically induced epilepsy in rodents. In addition, based on recent electrophysiological data suggesting that TPM may interact with L-type Ca(2+) channels, we evaluated the effects of a concomitant administration of L-type Ca(2+) channel modulators on TPM's antiepileptic properties. TPM, dose-dependently, protected against audiogenic seizures in DBA/2 mice. Concomitant treatment with TPM and a low dose of L-type Ca(2+) channel antagonists nifedipine or verapamil or with the L-type Ca(2+) channel agonist, S(-)-1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)phenyl]-3-pyridinecarboxylic acid methyl ester (Bay k 8644) was able to increase the ED(50) for this drug. TPM also protected against seizures induced by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), 4-aminopyridine (4-AP) and pentylenetetrazole (PTZ), but this activity was not significantly modified by nifedipine. TPM, dose-dependently, reduced the number and duration of epileptic spike-wave discharges (SWDs) both in WAG/Rij rats and lethargic (lh/lh) mice, two genetic models of absence epilepsy. Nifedipine decreased TPM's activity in WAG/Rij rats but paradoxically enhanced it in lh/lh mice, whereas Bay k 8644 displayed opposite effects in both absence models. These results confirm TPM's broad spectrum of anticonvulsant activity and support the proposal that a modulation of neuronal L-type Ca(2+) channel activity plays an important role in its antiepileptic activity.

Animals↗
PubMed2006

A profile of alternative RNA splicing and transcript variation of CACNA1H, a human T-channel gene candidate for idiopathic generalized epilepsies.

Highly alternatively spliced genes may provide complex targets for disease mutations. Structural changes created by missense mutations may differentially affect the activity of alternative gene products, whereas missense, silent and non-coding mutations may alter developmental regulation of splice variant expression. CACNA1H is a human gene encoding Ca(v)3.2 low-voltage-activated, T-type calcium channels associated with bursting behavior in neurons and has been linked to more than 30 mutations apparently predisposing to childhood absence epilepsy (CAE) and other idiopathic generalized epilepsies (IGEs). Biophysical properties, including the effects of missense mutations, have been evaluated previously for a single splice form of Ca(v)3.2 expressed in transformed cell lines. We here show that CACNA1H is alternatively spliced at 12-14 sites, capable of generating both functional and non-functional transcripts. Variable cytoplasmic and extracellular protein domains point to likely differences in gating behavior, sensitivity to neuromodulation and interactions with extracellular matrix. Biophysical profiles of selected physiological Ca(v)3.2 forms reveal variations in kinetics and steady-state gating parameters, most likely to affect membrane firing. These were comparable to or larger than changes reported for previously studied mutations. Missense CAE and IGE mutations were clustered near segments associated with anomalous splicing. Missense and silent mutations were found to destroy, create or change the regulatory specificity of predicted exonic splicing enhancer sequences that may control splicing regulation. We discuss a paradigm for CACNA1H expression of Ca(v)3.2 subunits, which may influence future basic and clinical studies.

Alternative Splicing↗
PubMed2003

Review of lamotrigine and its clinical applications in epilepsy.

Lamotrigine is an anti-epileptic agent with broad efficacy. Lamotrigine works at voltage-sensitive sodium channels, thereby stabilising the neuronal membrane and inhibiting the release of excitatory neurotransmitters such as glutamate and aspartate. Early preclinical animal studies indicate its broad-spectrum efficacy, which was later confirmed in clinical trials. Multiple randomised, placebo-controlled and comparative trials demonstrate its efficacy against partial and secondarily generalised seizures. Open-label trials show its efficacy against generalised seizures, especially absence seizures of childhood absence epilepsy and generalised seizures of juvenile myoclonic epilepsy. Lamotrigine has a wide clinical dose range and possesses favourable pharmacokinetic properties. It has a good tolerability and safety profile, which enhance compliance. Its small risk of serious skin rash should be weighed against its potential benefits when choosing lamotrigine on an individual basis. Lamotrigine is an excellent therapeutic option in epilepsy.

Abnormalities, Drug-Induced↗
PubMed2002

Death in children with epilepsy: a population-based study.

BACKGROUND: Families of children with newly diagnosed epilepsy worry about death during a seizure. We aimed to assess the frequency and causes of death of children with epilepsy. METHOD: We did a population-based cohort study. The Nova Scotia epilepsy cohort includes all children who developed epilepsy during 1977-85. In 1999, we matched names and birth dates with provincial health-care, death, and marriage registries. We examined death certificates, necropsy reports, and physician records of children who had died and contacted families if sudden unexpected death in epilepsy could have occurred. We measured the effect of sex, age, epilepsy type, and disorder sufficient to cause functional neurological deficit on death rate. We compared cohort mortality with rates in a reference population matched for age and sex. FINDINGS: 26 (3.8%) of 692 children with epilepsy died. Frequency of death was 5.3 times higher (95% CI 2.29-8.32) than in the reference population in the 1980s and 8.8 times higher (4.16-13.43) in the 1990s. Kaplan-Meier curves showed 6.1% mortality 20 years after onset compared with 0.88% in the reference population. Deaths occurred in one (1%) of 97 children with absence epilepsy, 12 (2%) of 510 with partial and primary generalised epilepsy, and 13 (15%) of 85 with secondary generalised epilepsy. 22 deaths were caused by disorders sufficient to cause functional neurological deficit, one by probable sudden unexpected death in epilepsy, two by suicide, and one by homicide. Functional neurological deficit was the only independent determinant of mortality. INTERPRETATION: Death from epilepsy is uncommon in children without a severe neurological disorder sufficient to cause functional neurological deficit and sudden unexpected death in epilepsy is rare.

Adolescent↗
PubMed2002

Seizure-related injuries in children with newly diagnosed and untreated epilepsy.

PURPOSE: Patients with epilepsy are reported to have an increased risk of physical injury. One of clinicians' concerns for diagnosing epilepsy early is to try to prevent such injuries and also to allay parental anxiety that seizures may cause injuries. The purpose of this study was to investigate injuries in children with newly diagnosed epilepsy and before starting antiepileptic medication. METHODS: A prospective study was undertaken of all newly diagnosed and untreated patients with at least two unprovoked, afebrile seizures of any type, aged 1-16 years, presenting consecutively to seven paediatric/paediatric neurology outpatient departments over a 12-month period. Information was collected on the duration of epilepsy before diagnosis, the epilepsy syndrome, the seizure type causing the injury, how and the age at which the injury was sustained, and whether hospital treatment was required for the injury. RESULTS: One hundred ninety-eight patients (116 boys) were surveyed. No patient died as a result of an injury. Twenty-five (12.6%) children experienced an injury before the diagnosis of epilepsy was established. Only four of the 25 patients (2% of all 198 patients) required medical attention for the injury. The injuries occurred at a mean age of 10.3 years (range, 4-15.1 years), and epilepsy was diagnosed at a mean age of 11.1 (range, 4.2-15.8) years. Fifteen patients were injured at home, six at school, and four outside the home. The seizures causing the injuries were tonic-clonic (17), complex partial (four), myoclonic (one), and of uncertain type (three). None of the 32 patients with childhood-onset typical absence epilepsy had accidental injuries. CONCLUSIONS: Injuries caused by epileptic seizures were uncommon in this newly diagnosed and untreated, consecutive paediatric outpatient series. These unique data could help to reassure clinicians that the diagnosis of epilepsy should not be influenced by any concern that accidental injuries caused by seizures are common in children before starting medication.

Accidents↗
PubMed2006

Dynamics of epileptic phenomena determined from statistics of ictal transitions.

In this paper, we investigate the dynamical scenarios of transitions between normal and paroxysmal state in epilepsy. We assume that some epileptic neural network are bistable i.e., they feature two operational states, ictal and interictal that co-exist. The transitions between these two states may occur according to a Poisson process, a random walk process or as a result of deterministic time-dependent mechanisms. We analyze data from animal models of absence epilepsy, human epilepsies and in vitro models. The distributions of durations of ictal and interictal epochs are fitted with a gamma distribution. On the basis of qualitative features of the fits, we identify the dynamical processes that may have generated the underlying data. The analysis showed that the following hold. 1) The dynamics of ictal epochs differ from those of interictal states. 2) Seizure initiation can be accounted for by a random walk process while seizure termination is often mediated by deterministic mechanisms. 3) In certain cases, the transitions between ictal and interictal states can be modeled by a Poisson process operating in a bistable network. These results imply that exact prediction of seizure occurrence is not possible but termination of an ictal state by appropriate counter stimulation might be feasible.

Adolescent↗
PubMed1989

Genetic aspects of childhood epilepsy.

The extensive studies pertinent to these problems cannot be elaborated here. We have restricted ourselves to a few representative concepts, which can be summarized as follows. The genetic aspects of convulsibility and epilepsy are highly complex phenomena. The level of convulsibility is determined by a number of different excitatory (and inhibitory) genetic factors. None of these factors is strictly specific to epilepsy. Each one is only a partial aspect of a complex genetic constitution which is strikingly common in perfectly healthy individuals, and which is related to a variety of psychic and somatic particularities. Almost all of these genetic factors seem to be polygenetically determined; in other words, they seem to reflect the actions of many genes. An increased liability to convulsions, and, finally, to epilepsy, is induced by an accumulation of these factorial sets, and, of course, by the effects of exogenous lesional factors. Special constellation of these polygenic sets may lead to the manifestation of different epileptic syndromes and may also explain the segregation of seizure types in the descendants of patients with seemingly uniform epileptic syndromes, as observed, for instance, in absence epilepsy and in juvenile myoclonic epilepsy.

Child↗
PubMed2004

Gamma rhythms are not integral to EEG spindle phenomena.

OBJECTIVE: Gamma rhythms (30-100 Hz) have been shown to be associated with spindling activity induced by picrotoxin. To determine if gamma power is unique to picrotoxin spindles or is an integral part of physiological and pathological spindling activity we analysed and compared the strength and brain distribution of gamma EEG power during 4 spindling activities in the rat. METHODS: The electroencephalogram (EEG) was recorded from rats with chronically implanted electrodes during natural sleep, barbiturate anaesthesia, during naturally occurring absence epilepsy spike and wave discharges and following the systemic application of picrotoxin. Spectral analysis was applied off-line to compare the strength and brain distribution of gamma EEG power during the 4 spindling activities. RESULTS: Each spindle type contained significantly different levels of gamma power. Gamma power was significantly increased over background levels during picrotoxin spindles, slightly increased during absence spindles, slightly decreased during sleep spindles and significantly suppressed during barbiturate spindles CONCLUSIONS: Changes in the power of gamma frequencies during spindle types suggest that gamma frequencies are neither the cause of nor an integral part of a spindle. They appear to be correlated with levels of consciousness and may contribute to the process of epileptogenesis. SIGNIFICANCE: The findings are consistent with high frequency EEG activity being related to seizure-tendency.

Animals↗
PubMed2005

Validation of a method for localised microinjection of drugs into thalamic subregions in rats for epilepsy pharmacological studies.

OBJECTIVES: To validate a method for the chronic implantation of micro-cannulae to examine the effect of drug administration to two small brain regions critical to the control of generalised seizures, the reticular nucleus of the thalamus (Rt) and the ventrobasal thalamus (VB), in a genetically epileptic rat model. METHOD: Micro-cannulae guides (length 9 mm, 26G, i.d. 0.24 mm, o.d. 0.46 mm) were implanted bilaterally into either the Rt or the VB of 11- to 13-week-old Genetic Absence Epilepsy Rats from Strasbourg (GAERS) using a stereotaxic head frame. After a seven-day recovery period the animals were injected with 0.2 microl of methylene blue. The animals were allowed to move freely in their cages for a further 90 min while a post-drug EEG recording was acquired and then brains were perfused with 4% paraformaldehyde and extracted. Twenty-micrometer slices were cut on a cryostat and the site and extent of the methylene blue staining in the brain determined. The implantation co-ordinates were adjusted accordingly, and then a validation study was performed on a further cohort of rats (n=8 Rt, n=7 VB). RESULTS: The co-ordinates that were found to most accurately localise the Rt were: AP -3mm, ML 3.6mm, DV -5.8mm (relative to Bregma). Those that accurately localised the VB were: AP -3mm, ML 2.6mm, DV -5.5mm. In the validation study, the dye staining was measured to diffuse an average radius of 520+/-120 microm from the centre of the injection site for the 0.2 microl injection in both brain hemispheres. For the VB injections the dye remained confined within the structure, however, for the smaller Rt there was spread to surrounding structures in the axial plane. The radial diffusion for the 0.5 microl injection was similar, but more of the dye was found to spread back up the cannula tract away from the target zone. CONCLUSION: These studies have validated a method for accurate and localised injection of drugs into the VB and Rt for neuropharmacological studies in a rat model of generalised epilepsy. This method allows the measurement of localised drug effects on EEG and generalised seizure activity at these sites.

Animals↗