Amino acid content of the brain in rats focal penicillin induced epilepsy.

The initial objective of the present study was to investigate the role of excitatory and inhibitory amino acids in generalized as compared to focal epilepsy, both forms being induced by the same convulsant agent, i.e. penicillin. Our attempts to obtain in the rat the generalized epilepsy, constantly induced in cats by systemic administration of penicillin, were unsuccessful. This is probably due to the rudimentary development of the cerebral cortex in rodents as compared to the feline cortex. The tentative conclusion was drawn that the cortex is the brain structure mainly involved in the genesis of petit mal seizures. Penicillin was applied to the cortex of 40 white Wistar rats and the electrical cortical activity was registered. The concentrations of glutamate, aspartate, glycine, GABA and serine were determined in the cerebral cortex, the brain stem and the cerebellum. The same amino acids were determined in the brain of 20 controls. No significant changes in the amino acid contents were obtained in the cerebral cortex. In the brain stem the glutamate level was significantly increased while the glycine content was markedly decreased. These findings are consistent with the involvement of the brain stem structures in seizure activity.

Habituation of orienting reaction in therapy-resistant partial epilepsy.

A polygraphic study on resistance to habituation of the somatic, autonomic and EEG components of the orienting reaction elicited by a repetitive auditory stimulus was performed in 66 epileptics with therapy-resistant partial seizures (TRPS) and in 135 matched subjects in two control groups. The study showed a significantly higher resistance to habituation of the orienting reaction in epileptics with TRPS vs. the normal subjects of the control group I. A significantly higher resistance to habituation was also noted vs. the epileptics with therapy-controlled partial seizures of control group II. The correlational analysis of data showed that the severity of these habituation disturbances in epileptics with TRPS depended on the patients' age, type of electroclinical seizures, pretrial seizure frequency, type of resting EEG, administered treatment (no. of administered antiepileptic drugs/patient), daily dose, as well as on the serum level of these drugs. The multivariate regression analysis showed that the most significant predictive variables for the habituation disturbances were the pretrial seizure frequency, type of electroclinical seizures, daily dose of administered antiepileptic drugs and their serum level. The data also evidenced that the antiepileptic treatment improves the interictal habituation disturbances, the effect being more marked as the treatment was more sustained. The above-mentioned habituation changes in epileptics with TRPS should be ascribed to some disturbances in nervous excitability.

Increased susceptibility to audiogenic seizures following withdrawal of progesterone.

This investigation was performed to verify a previous hypothesis which correlates the catamenial seizures with the stoppage of progesterone secretion. White rats from a Wistar strain were tested with an electric bell. Thirty-five animals refractory to the acoustic stimulus were selected for the experiment. Each animal received 9 daily injections with progesterone, 5 mgr/day. The animals were tested with the acoustic stimulus after the 5th and the 9th injections, 24 hours after the administration of the last dose. Audiogenic seizures were obtained in 29.4% of the rats tested after 5 injections and in 40.0% of the rats tested after the 9th injection. The increased seizure susceptibility lasted 3-8 days after the hormone withdrawal. In conclusion, the withdrawal of high doses of progesterone exerts a seizure-activating effect.

The cerebral content of excitatory and inhibitory amino acids in rats following withdrawal of antiepileptic drugs.

The aim of the present study was to investigate the role of amino acids in the increased seizure susceptibility induced by withdrawal of antiepileptic drugs (AEDs). Fifty white Wistar rats treated with AEDs and 30 controls were used. The animals were previously exposed to the acoustic stimulus and only the non responsive were used. The administered AEDs were morphosuximide, ethosuximide, phenobarbital, valproate and gluthetimide. The treatment was discontinued after 2 weeks. The acoustic stimulation was repeated after 2-4 days of abstention. The animals were sacrificed and the amino acids glutamate, aspartate, GABA, glycine and serine were determined in the cortex and the brain stem. The withdrawal of AEDs induced seizure susceptibility in 71% of the rats treated with phenobarbital and in 76% of those receiving morphosuximide. A significant increase of glutamate levels was found in the brain stem following withdrawal of both morphosuximide and ethosuximide. The level of GABA was elevated in the brain stem after valproate and morphosuximide withdrawal. The increase of glutamate concentration can be correlated with the increased seizure susceptibility. The unexpected rise of the GABA level could be interpreted as a compensatory inhibitory mechanism.

Interictal responsiveness in therapy-resistant partial epilepsy.

A polygraphic study of the somatic, autonomic and EEG components of the orienting reaction elicited by an auditory stimulus was performed in 66 epileptics with therapy-resistant partial seizures (TRPS) and in 135 matched subjects in two control groups. The study showed a significant interictal hyperresponsivity in epileptics with TRPS vs. the normal subjects of control group I, which consisted in a marked increase of the intensity of the orienting reaction components. This hyperresponsivity was also more marked than that noted in epileptics with therapy-controlled partial seizures of control group II. The correlational analysis of data showed that the severity of these responsiveness disturbances in epileptics with TRPS depended on the patients' age, type of electroclinical seizures, pretrial seizure frequency, type of resting EEG, administered treatment (no. of administered antiepileptic drugs/patient), daily dose, as well as on the serum level of these drugs. The multivariate regression analysis showed that the most significant predictive variables for the responsiveness disturbances were the pretrial seizure frequency, type of electroclinical seizures, daily dose of administered antiepileptic drugs and their serum level. The data also evidenced that the antiepileptic treatment improves the interictal responsiveness disturbances, the effect being the more marked as the treatment was more sustained. The above-mentioned responsiveness changes in epileptics with TRPS should be ascribed to some disturbances in nervous excitability.

Terminal complement complex in blood of patients with neurological diseases.

The local involvement of complement (C) in the pathophysiology of tissue lesions in several neurological diseases is known, but it has never been studied whether or not in neurological disorders the C activity in the circulation is altered as well. This was the aim of the present investigations. We measured in blood plasma, with an automatic device for analysis and quantitation of the haemolytic activity of the terminal complement complex, the variables T1, T2 and T3 which define the latter quantitatively. We did this, on the one hand, in 100 patients who had 46 neurological disorders systematized in 16 nosological groups, and, on the other hand, in a control group of 40 healthy blood-donors. The mean values of all variables found in the patients have not been statistically different from those found in the controls. This demonstrates that in neurological disorders possible activations of C remain restricted to the local tissue lesions and do not occur in blood, probably due to the opposition against C activation of the known inhibitor system.

Carbohydrate metabolism, as reflected by glycosylated hemoglobin, in clinically active definite multiple sclerosis.

In 30 patients with the diagnosis of definite multiple sclerosis (MS) established on clinical criteria (CDMS-A1 patients), who were in a severe clinical state of MS, i.e., in whom one or more MS clinical signs or symptoms had become obvious during the last 10 days, the integrated concentration of plasma glucose over long-term (the last 6-8 weeks) was established by measurement of the percent of the glycosylated fraction of hemoglobin (Hb A1). This was also investigated in two control groups: CG-1, which consisted in 33 registered healthy blood donors matched for sex and age with the MS patients, and CG-2, consisting in 7 patients with diabetic neuropathy. The mean-value of Hb A1 of 5.1% (SD = 0.82) in the MS patients and that of 5.12% (SD = 0.96) in CG-1 controls are not statistically different (t = 0.09). The Hb A1 mean-value of 10.53% (SD = 3.5) found in the CG-2 controls is different (p < 0.001) from both the mean-values in MS patients and CG-1 controls, which validates the reliability of the HB A1 investigation. The findings indicate that clinical activation in definite MS is not associated with disturbances of glucose metabolism.

Habituation of orienting reaction in therapy-resistant generalized epilepsy.

A polygraphic study on resistance to habituation of the somatic, autonomic and EEG components of the orienting reaction elicited by a repetitive auditory stimulus was performed in 39 epileptics with therapy-resistant generalized seizures (TRGS) and in 119 matched subjects in two control groups. The study showed a significantly higher resistance to habituation of the orienting reaction in epileptics with TRGS vs. the normal subjects of control group I. A significantly higher resistance to habituation was also noted in epileptics with therapy-controlled generalized seizures of control group II. The correlational analysis of data showed that the severity of these habituation disturbances in epileptics with TRGS depended on the patients' age, type of electroclinical seizures, pretrial seizure frequency, type of resting EEG, administered treatment (no. of administered antiepileptic drugs/patient), daily dose, as well as on the serum level of these drugs. The multivariate regression analysis showed that the most significant predictive variables for the habituation disturbances were the pretrial seizure frequency, type of electroclinical seizures, daily dose of administered antiepileptic drugs and their serum level. The data also evidenced that the antiepileptic treatment improves the interictal habituation disturbances, the effect being the more marked as the treatment was more sustained. The above-mentioned habituation changes in epileptics with TRGS should be ascribed to some disturbances in nervous excitability.

Lidocaine kindling does not generate epilepsy.

Forty Wistar rats were injected with a solution of lidocaine (90 mg/kg s.c.) 5 days per week for 30-40 days. In 36 of the animals, attacks of stiffness were obtained. After a period of disordered movements, the animals, remained completely immobile with the hindlimbs rigidly extended. The attacks of stiffness lasted from 10 to 60 minutes. The hemisection of the spinal cord at the thoracic level suppressed the rigidity of the ipsilateral leg. Electrical recording with electrodes applied to the cortex or implanted in the depth of the temporal lobe failed to reveal paroxysmal activity. These data could not confirm the results of other authors reporting typical epileptic seizures after lidocaine kindling. Despite essential differences, epileptic kindling and lidocaine-kindled stiffness attacks are both manifestations of the central nervous system plasticity. Therefore it appears that pharmacologically induced plasticity is a more general process than epileptic kindling.

Early prognosis of survival or death after a recent stroke by blood levels of acute-phase proteins.

From 129 patients with a recent stroke 105 survived and 24 died within 3 weeks from stroke-onset. At around 40 hours after the latter, the blood-levels of the acute-phase proteins ceruloplasmin and albumin did not forecast the death of the respective patients, but, in contradistinction, the level of fibrinogen was significantly higher in those who eventually died, than in those who survived. Therefore, a higher level of fibrinogen could be a risk-factor for death after stroke.

Acute-phase proteins in stroke: influences of its cause (cerebral hemorrhage or infarction), of the cerebral site of infarction, and of the sex of patients.

In most of the 129 patients with a recent stroke by cerebral hemorrhage or infarction a note-worthy acute-phase response was found, as demonstrated by important quantitative alterations of blood levels of several acute-phase proteins (APP). These alterations were different in patients with cerebral hemorrhage as compared to those with cerebral infarction. The alterations due to cerebral infarction were not different according to the site of the infarction in brain, i.e. in the brain territories irrigated by the carotid artery system or by the basilar artery system. The APP alterations do not depend on the sex of patients or on the time elapsed from stroke-onset to blood collection.

Orienting reaction in therapy-resistant generalized epilepsy.

A polygraphic study of the somatic, autonomic and EEG components of the orienting reaction elicited by an auditory stimulus was performed in 39 epileptics with therapy-resistant generalized seizures (TRGS) and in 119 matched subjects in two control groups. The study showed a significant interictal hyperresponsivity in epileptics with TRGS vs. the normal subjects of control group I, which consisted in a marked increase of the intensity of the orienting reaction components. This hyperresponsivity was also more marked than that noted in epileptics with therapy-controlled generalized seizures of control group II. The correlation analysis of data showed that the severity of these responsiveness disturbances in epileptics with TRGS depended on the patients' age, type of electroclinical seizures, pretrial seizure frequency, type of resting EEG, administered treatment (no. of administered antiepileptic drugs/patient), daily dose, as well as on the serum level of these drugs. The multivariate regression analysis showed that the most significant predictive variables for the responsiveness disturbances were the pretrial seizure frequency, type of electroclinical seizures, daily dose of administered antiepileptic drugs and their serum level. The data also evidenced that the antiepileptic treatment improves the interictal responsiveness disturbances, the effect being the more marked as the treatment was more sustained. The above-mentioned responsiveness changes in epileptics with TRGS should be ascribed to some disturbances in nervous excitability.

Brain amino acid levels in audiogenic seizure-susceptible rats following habituation to the auditory stimulus.

Hippocampic and brain stem levels of amino acids were determined in audiogenic seizure-susceptible rats following habituation by repeated exposure to the acoustic stimulus. The biochemical determinations were performed in the brains of 42 habituated animals and 23 not habituated seizure susceptible rats used as controls. It was found that the habituation process is associated with: a) increased levels of aspartate in hippocampus and pons; b) significantly decreased levels of glycine in the hippocampus and pons; c) decreased concentration of glutamate in the pons; d) no significant changes in the GABA concentrations in hippocampus and brain stem. The changes of the excitatory and inhibitory amino acids in the brain of the habituated rats cannot explain the fall in epileptic susceptibility associated with habituation.

Activity of some lysosomal enzymes and postnatal ontogenetic development of epileptic reactivity in rabbit brain.

The beta-glycerophosphatase (GP), p-nitrophenyl phosphatase (PNFP) and beta-glucuronidase (BG) activities in four neocortical rabbit areas have been determined in six successive electrocorticographic stages of postnatal ontogenetic development of epileptic reactivity. The lysosomal enzyme activity decreases gradually from rabbits aged 1 day to adult ones and is similar within the four neocortical areas. The activity of the three lysosomal enzymes is not parallel. Statistically significant decreases in beta-glycerophosphatase activity are present in rabbits at the age of 30 days versus adult age in all the areas investigated while beta-glucuronidase is higher at the same developmental stage only in beta retrosplenial (III) and motor (II) areas. Correlation of the electrophysiological and biochemical data cannot provide explanation for the particular phenomena of the epileptogenic reactivity in rabbit cerebral neocortex.