ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1994.tb02941.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Summary:Developments in magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and single photon emission tomography (SPECT) have opened new opportunities for noninvasive brain investigation. Functional imaging methods involving noninvasive MRI and minimally invasive PET and SPECT are available that allow investigation of brain abnormality in intractable epilepsy patients. Noninvasive techniques enable the investigation of many aspects of the underlying neuropathologic basis of intractable seizures and of the relationship of functional abnormalities both to structural abnormalities and to the seizure focus. New MRI techniques demonstrate the structure of the brain in fine detail (especially the hippocampus), provide information about the underlying metabolism of brain regions, and demonstrate functional activity of the brain with high spatial and temporal resolution. The clinical impact of this noninvasive information cannot be overstated and these techniques provide indispensable information to neurologists specializing in epi‐leptology. The proper use and interpretation of the findings provided by these new technologies will be a major challenge to epilepsy programs in the next few year

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1994.tb05985.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Summary:In the United Kingdom, the question of whether to commence antiepileptic drug (AED) treatment remains controversial. Surveys indicate that 15% of patients are treated after a first seizure. Pediatricians often wait for a third or fourth seizure before treating, whereas clinicians who deal with adult patients are more likely to intervene early, largely because of concerns about driving and employment. Monotherapy is becoming the rule for the majority of patients. The four primary AEDs in the United Kingdom are carbamazepine and phenytoin (˜ 30% each), valproate (VPA; ˜25%), and phenobarbital (˜ 18%). For partial epilepsies, studies show few major differences in efficacy among these four AEDs. A first‐line AED should be one, such as VPA, with a broad spectrum of activity that is easily managed by clinicians who may not have special expertise in the recognition of differing seizure types and epilepsy syndromes. Where differences in efficacy are marginal, comparative drug toxicity may be a major factor in AED selection. Most new AEDs have low toxicity profiles. With respect to discontinuation, pediatricians usually recommend a trial discontinuation period in most children who achieve a 1‐ or 2‐year remission of epilepsy. For adults, however, overall relapse rates after discontinuation are – 401‐50%; therefore, patients usually opt for long‐te

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1994.tb05954.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Summary:The antiepileptic drug (AED) oxcarbazepine (OCBZ) and its rapidly formed 10‐monohydroxy metabolite (MHD) protect against electroshock‐induced tonic hindlimb extension in rodents (ED5014–21 mg/kg p.o.). Both stereoisomers of MHD also protect. As with carbamazepine (CBZ), these findings suggest clinical efficacy against generalized tonic‐clonic and, to some extent, partial seizures. OCBZ (IC505 × 108M), MHD (IC502 × 10‐8M) and CBZ (IC506 × 10‐7M) limit the frequency of firing of sodium‐dependent action potentials by cultured mouse central neurons and reduceVmixprogressively in a use‐dependent manner at concentrations below therapeutic plasma concentrations in OCBZ‐treated patients. This suggests that blockade of voltagesensitive sodium channels could contribute to the antiepileptic efficacy of OCBZ. Blockade of penicillin‐induced epileptiform discharges in hippocampal slices by MHD and its stereoisomers was diminished when the potassium channel blocker 4‐aminopyridine was added to the bath fluid. This indicates that additional mechanisms of action, e.g., an effect on potassium channels, might be clinically important. In addition, both stereoisomers are equally responsible for the antiepileptic activity of the racemate, i.e., MHD, and are therefore likely to play a therapeutic role. Such actions could confer broad

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1994.tb05949.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Summary:The development of new antiepileptic drugs is poised on the cusp between empiricism and the rational scientific development of medicaments designed to perform specific neurophysiologic functions in keeping with modern ideas of epilepsy generation and spread. It takes into account the difference between seizures and their underlying disorder known as epilepsies and the fact that, although seizures can be effectively treated with pharmacologic agents, the development of epilepsy requires both a predisposition (which may be innate or preventable) and precipitating factors that determine the timing of the individual seizures. The local membrane phenomena or cellular substrates of epilepsy can be described, as can the process of epileptogenesis. New antiepileptic development can be viewed in the light of these concepts.

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1994.tb05971.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Summary:Convulsive epilepsies are generally unmistakable. Absence epilepsies, which are easily recognized by the provocation of an episode during hyperventilation and by the typical features of the EEG, can be overdiagnosed, especially in the child who daydreams in class and has scattered, asymptomatic, epileptogenic EEG changes. As in adults, complex partial seizures in children can be difficult to distinguish from certain behaviors. Several types of benign childhood epilepsies need to be distinguished from the more intractable and lesional childhood epilepsies. Two common examples, benign rolandic epilepsy and benign occipital epilepsy, can be recognized by their unique EEG changes and clinical features. Juvenile myoclonic epilepsy generally does not remit spontaneously but should be recognized because it appears to respond to valproate. Some recurrent nonepileptic events seen in children can be mistaken for seizures, including shuddering attacks, paroxysmal vertigo, breath‐holding spells, cardiogenic syncope, night terrors, and movement disorders, such as paroxysmal kinesigenic choreoathetosi

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1994.tb05936.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Summary:Presently, most strategies for development of antiepileptic drugs (AEDs) center around seizure models that are known to respond to presently marketed AEDs. These strategies do not take into account that epilepsy can be a progressive disease. Moreover, region‐specific aspects of ep‐ileptogenesis are rarely considered when new AEDs are developed. Seizures in the temporal lobe are often difficult to treat. Animal studies on various seizure models in the hippocampus and the entorhinal cortex (EC) suggest that these structures do not a priori produce seizures that are difficult to treat. However, seizure‐like events in the EC tend to progress to a state of status epilepticus‐like activity that cannot be suppressed by presently marketed AEDs. Loss of 7‐aminobutyric acid (GABA)ergic neurotransmission and increased excitatory synaptic coupling seem to cooperate for induction of this state. Epilepsy induced alterations in the interaction between the EC and the hippocampus may lead to alterations that facilitate precipitation of seizures. Because of the recurrent interaction between the hippocampus and the EC, these seizures may reach an intensity that is no longer controllable by presently available AEDs. Ontogenetic alterations of the circuitry between the EC and the hippocampus. seizure‐induced stabilization of synaptic connections over‐expressed during ontogenesis, seizure‐induced lesions and subsequent rearrangements of internal cell properties, and synaptic arrangements and kindling‐like alterations of nerve cell and glial behavior may all be involved in the generation of a neuronal aggregate whose balance between inhibitory and excitatory processes becomes readily disturbed. Strategies for the development of AEDs treating such seizures should suppress hyperactivity and prevent progression of epilepto‐genesis. AEDs directed against seizures may be effective if they can be given in sufficient concentrations to suppress very int

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1994.tb05959.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Summary:Antiepileptic drugs (AEDs) are administered to patients for acute and long‐term treatment of seizures. Most patients with acute convulsions receive intravenous (i.v.) benzodiazepine (BZD), frequently followed by i.v. loading with phenytoin (PHT), especially when seizures continue. For patients with absence status epilepticus, BZD is usually followed by ethosuximide (ESM) or valproate (VPA). The decision to continue AED therapy is based on the likelihood that seizures will continue or recur. Once epilepsy is diagnosed, long‐term treatment with AEDs is recommended, beginning with monotherapy. Two studies sponsored by the U.S. Veterans Administration (VA), which compared the efficacy of carbamazepine (CBZ), PHT, phenobarbital (PB), primidone (PRM), and VPA, recommend that most adults with recurrent partial seizures receive either CBZ or PHT. The 1992 VA study suggests that VPA is equal to CBZ or PHT in efficacy when partial seizures become secondarily generalized. Primary generalized epilepsies are most frequently treated with VPA when combinations of generalized seizures exist. ESM is prescribed most often when typical childhood absence seizures exist alone. Although many authorities do not recommend long‐term treatment of childhood febrile seizures, PB is administered by some when febrile seizures have complex symptomatology. In general, AED monotherapy is currently preferred, but those with more refractory epilepsy receive polytherapy. CBZ, PHT, PB, PRM, VPA, and ESM are the primary AEDs prescribed in the United States. PHT, followed by CBZ and VPA, is the most frequently prescribed AED as both new and total prescriptions. The introduction of fel‐bamate, gabapentin, and lamotrigine may alter these patterns in the

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1994.tb05951.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Summary:To elucidate the consequences of convulsions, we examined biochemically and electrophysiologically the brains of mice that had sustained two complete tonicclonic convulsions after administration of pentylenetetrazol (PTZ 50 mg/kg intraperitoneally, i.p.), 48 and 24 h before decapitation. Control mice were injected with saline. Input/output curves of the extracellular synaptic responses in the CAI area of hippocampal slices showed that PTZ‐induced seizures do not establish the persistent change in hippocampal excitability itself that can be detected in vitro. However, use of the paired‐pulse stimulation paradigm showed that γ‐aminobutyric acid, (GABA)‐mediated recurrent inhibition was significantly weaker (by 19–25%) in the CA1 area of slices from PTZtreated mice (PTZ slices) as compared with slices from control mice (control slices). The density of GABA, receptors (high‐affinity component) was also lower in hippocampus (by 19%) and cortex (by 14%) of PTZ‐treated mice. A GABA‐related disinhibitory mechanism underlying PTZ seizures may thus persist for 1 day after the seizure, predisposing the brain to subsequent seizures. On the other hand, the depressant effect of a single dose of adenosine 10 μMon the CA1 synaptic response was stronger (by 35% on population spikes) and longer lasting in PTZ slices as compared with controls. This could be attributed to significantly higher adenosine A1receptor density in hippocampus (Bmaxof [3H]CHA was higher by 34%) as well as cortex and cerebellum of these animals. The phenomenon may reflect an adenosine A1‐mediated adaptive mechanism that offers protection from

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1994.tb02906.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Summary:Magnetic resonance spectroscopy (MRS) can be used for noninvasive measurement of more than two dozen small metabolites in the brains of living animals and humans. In the first decade of its use for study of seizure phenomena in animals, MRS successfully detected in vivo seizure‐induced cerebral acidosis and reduction of phosphocreatine concentration, changes that had been described previously by techniques requiring destruction of tissue. Thus validated, MRS was used to reveal new aspects of epileptic pathophysiology in animals: (a) dissociation of brain lactate and pH during experimental status epilepticus of low and intermediate intensity, reflecting metabolic compartmentation; and (b) long persistence of metabolically active elevated brain lactate after brief cortical electroshock. The latter phenomenon may be an extreme form of a mechanism by which lactate production primes synaptic terminals for maximal sustained firing rates during normal brain activation. Diffusion‐weigh ted imaging of rat brain has shown that status epilepticus apparently shortens the mean path length of water diffusion, a novel finding that provides new insight concerning the physical conditions under which the seizure‐related chemical changes detected by MRS occur. MRS study of epileptic patients has been undertaken more recently as instruments large enough for observations on humans have become available. Acidosis, reduction of phosphocreatine, and elevation of lactate have all been demonstrated in the human brain during seizure discharge. Chronic reduction of N‐acetylaspar‐tate in limbic regions probably reflects neuronal loss and may correlate with mesial temporal

ISSN:0013-9580    

DOI:10.1111/j.1528-1157.1994.tb05984.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY