Maria Rita de Feo

Autosomal Dominant Lateral Temporal Epilepsy: Clinical Spectrum, New Epitempin Mutations, and Genetic Heterogeneity in Seven European Families

Summary:  Purpose: To describe the clinical and genetic findings of seven additional pedigrees with autosomal dominant lateral temporal epilepsy (ADLTE).

Long‐Term Effects of Early Status Epilepticus on the Acquisition of Conditioned Avoidance Behavior in Rats

Summary: The acquisition of active avoidance behavior in a shuttle‐box apparatus was studied in 45‐day‐old rats. In these animals a single episode of status epilepticus had been induced by the systemic administration of kainic acid (KA) or pentylenetetrazole (PTZ), when they were 10 or 25 days old. The results were compared with those obtained from animals in which, at the same ages, only saline solution had been injected. In KA‐treated rats a decrement of right responses and a prolonged reaction time were observed, with these results more evident in animals treated earlier (10 days). Parallel with the behavioral alterations, the histological, morphometric and morphological examinations revealed neuronal and glial abnormalities at the neocortical level, while no lesions were found in the hippocampus. PTZ‐treated rats showed no behavioral alteration nor histological abnormality. The different findings obtained after KA and PTZ injection suggest that not only status epilepticus per se, but the mechanism of action and the neurotoxicity of the convulsant agent, are very important in impairing late performances.

Clinical and Electroencephalographic Effects of Topiramate in Patients with Epilepsy and Healthy Volunteers

Although topiramate, one of the newer drugs used in treating epilepsy, is effective in reducing seizure frequency and has a wide spectrum of action, it often induces intolerable adverse effects, predominantly related to the central nervous system. Information that would help document adverse reactions early, thus allowing topiramate doses to be adjusted during the drug titration and maintenance phases, could be obtained from electroencephalogram (EEG) studies. We studied the clinical effects and EEG changes induced by topiramate in patients with refractory partial epilepsy receiving the drug as add-on therapy. To exclude effects related to the other drugs and to epilepsy itself, we compared data from patients and healthy volunteers. After receiving topiramate, 22.6% of patients became seizure free and 29% had their seizures reduced by 50% or more. Topiramate nevertheless induced noteworthy adverse reactions, the main problems being sedative and cognitive changes. Also, in healthy volunteers, a single 100-mg dose of topiramate induced mild adverse reactions, mainly affecting concentration and attention, with difficulties in speech and writing. In patients with epilepsy, the EEG changes induced by topiramate consisted of increased delta and theta activities and decreased activity in the rapid bands. This recognizable topiramate-induced EEG pattern was again evident in the healthy volunteers, in whom we also detected a significant reduction in the alpha frequency rhythm. Our results confirm that topiramate needs to be introduced gradually while patients undergo close neuropsychologic and neurophysiologic monitoring to detect adverse sedative and cognitive reactions early. The EEG correlate of these events seems to be increased activity in the slower frequency bands.

Effects of γ-Globulin Therapy in Severely Epileptic Children

Summary: The effects of γ‐globulin therapy have been studied from clinical, immunological, and electrographic perspectives in 10 children affected by severe organic epilepsy. After the first or the second injection of large doses of IgG, an appreciable reduction in seizure frequency and an improvement in behavioral and psychological performance were observed in seven children. These clinical modifications were not correlated with an important decrease of the EEG epileptic elements, but in most cases they were associated to an increase in α activity and/or in power of the predominant EEG frequency. These changes were observed during the entire treatment period and tended to disappear when therapy was interrupted. No significant changes in both immunological data and plasma levels of antiepileptic drugs accompanied the clinical and EEG changes.

Prenatal cocaine: Seizure susceptibility in rat offspring

Proconvulsant and convulsant effects of cocaine have been described in various experimental models of epilepsy. We have studied the susceptibility to bicuculline and pentylenetetrazol-induced seizures in developing 10-, 20- and 30-day old rats, gestationally exposed to cocaine. Incidence and latency of appearance of the epileptic manifestations, their evolution toward status epilepticus and successive recovery or death, have been evaluated and compared to the same parameters obtained in control animals of the same ages. Results have demonstrated that 10-day-old rats that had been exposed to cocaine are significantly less sensitive than control animals to the convulsant action of both bicuculline and pentylenetetrazole while no substantial differences between the two groups have been found at the successive ages. It is possible that modifications of various neurotransmitter systems caused by prenatal cocaine exposure modify neuronal excitability at least at early stages of development.

A simple method for implanting electrodes in freely moving neonatal rats.

A simple method for implanting cortical and subcortical electrodes in very young rats is described, which does not interfere with the behavior of the animal during the experiment. The cortical electrodes are anchored to the skull by a spiral whose first loop is introduced between the inner layer of the skull and the dura mater. The subcortical electrodes have a loop which rests above the skull. Both the spirals of the cortical electrodes and the loops of subcortical electrodes are then embedded in dental acrylic.

Age-related anticonvulsant activity of NMDA in the rat caudate-putamen

Striatal pathways are important for modulating the threshold for seizures in the rat forebrain. N-Methyl-D-aspartate (NMDA), an excitatory amino acid derivative and powerful anticonvulsant agent, when injected into the brain, has been shown to protect adult rats against kindling and pilocarpine-induced seizures when injected into the caudate-putamen. The present study examines whether the anticonvulsant action of NMDA in the caudate-putamen varies with age. Bilateral striatal administration of NMDA was effective in suppressing bicuculline-induced seizures in rats older than 23 days of age. The results suggest that striatal pathways involved in the anticonvulsant activity of NMDA in the caudate-putamen are not functionally active in developing rats before the 4th week of life.

Effects of carbamazepine on bicuculline- and pentylenetetrazol-induced seizures in developing rats

The anticonvulsant effect of carbamazepine (CBZ) was examined in 10-, 18- and 25-day-old Wistar albino rats into which bicuculline or pentylenetetrazol had been systemically injected to induce generalized epileptic manifestations typical for the specific age of the animals. The results showed that: a) in developing rats, CBZ appears to be more effective in the pentylenetetrazol than the bicuculline model of epilepsy; b) in both models of epilepsy the efficacy of CBZ increases with the age of the animals; and c) among the various epileptic manifestations, the tonic phase is the most sensitive to the anticonvulsant effect of CBZ. These conclusions are correlated with the different levels of cerebral maturation of the animals, and are discussed with reference to the mechanisms of action of CBZ and bicuculline or pentylenetetrazol.

Penicillin epilepsy in the rabbit

Abstract The effects of penicillin perfusion were studied in 16 rabbits with chronically implanted electrodes in the sensorimotor and in the visual cortex of both hemispheres. In 14 rabbits, at an average dose of 1,279,966 IU/kg, penicillin caused the appearance of generalized spikes or polyspikes accompanied by massive myoclonic jerks. Sometimes massive myoclonic jerks without EEG epileptic activity were seen. In one animal only spinal myoclonic activity without EEG epileptic abnormalities occurred. Three of these rabbits developed, after a mean penicillin dose of 2,193,174 IU/kg, generalized seizures accompanied on the EEG by bilateral and synchronous discharges of spike or polyspike and wave complexes. The effect of penicillin was tested also in a group of four rabbits in which a small cortical vascular lesion was made, and in another group of four animals with electrodes implanted into the hippocampus. Rabbits with a vascular lesion and those with hippocampal electrodes developed a focal epilepsy at a mean dose of 1,286,804 IU/kg. In the rabbits with the cortical lesion, the seizures started always from the site of the lesion. In the group of animals with the hippocampal electrodes, the seizures could begin, even in the same rabbit, from the hippocampus or from the cortex over the implanted electrode. Penicillin in the rabbit produces a predominantly myoclonic form of seizure disorder and only rarely organized generalized seizures similar to those observed in the cat. Under circumstances in which a local breakdown of the blood-brain barrier has been created, it induces focal seizure discharges that become often secondarily generalized.