[Causes, diagnosis and treatments of circulatory shocks]. / États de choc : grands cadres étiologiques, prise en charge initiale.

Shock states are the leading causes of intensive care admission and are nowadays associated with high morbidity and mortality. They are driven by a complex physiopathology and most frequently a multifactorial mechanism. They can be separated in whether a decrease of oxygen delivery (quantitative shock) or an abnormal cell distribution of cardiac output (distributive shock). Septic, cardiogenic and hypovolemic shocks represent more than 80% of shock etiologies. Clinical presentation is mostly characterized by frequent arterial hypotension and sign of poor clinical perfusion. Hyperlactatemia occurs in most of shock states. The diagnostic of shock or earlier reversible "pre-shock" states is urgent in order to initiate adequate therapy. Therefore, orientation and therapies must be discussed with intensive care physiologists in a multidisciplinary approach. Etiologic investigation and correction is a primary concern. Hemodynamic and respiratory support reflect another part of initial therapy toward normalization of cell oxygenation. Fluid resuscitation is the corner stone part of initial therapy of any form of shock. Vasoconstrictive drugs or inotropic support still often remain necessary. The primary goal of initial resuscitation should be not only to restore blood arterial pressure but also to improve clinical perfusion markers. On the biological side, decrease of lactate concentration is associated with better outcome.

[Image guidance for the evaluation of setup accuracy]. / Imagerie de contrôle de positionnement : quelle fréquence pour quel objectif ?

Information obtained by different methods of image-guided radiotherapy now allows us to reposition the target volume. This evolution causes a change in practice and positioning control. In order to control positioning errors, a systematic control during the first three to five sessions is required. Random repositioning errors and clinical target volume motions can be mastered only by performing a daily imaging. Finally, image-guided radiotherapy allows assessing anatomical changes occurring during treatment, and opens the field of adaptive radiotherapy.

[Supra- and infraclavicular lymph node irradiation in breast cancer patients: state of the art]. / Radiothérapie des aires ganglionnaires sus- et sous-claviculaire dans les cancers du sein : état des lieux.

Radiation therapy plays an essential role in the treatment of invasive breast cancer. However, prophylactic treatment of supra- and infraclavicular lymph nodes is not consensual, with different treatment depending on the centres and practitioners. Clinical indications for radiotherapy of the supra- and infraclavicular lymph nodes are often the subject of a consensus. Nevertheless, radiotherapy induces some toxicity. Various techniques have been developed. To date, conformal radiotherapy allows an accurate assessment of doses to target volumes and organs at risk, but at the cost of a sometime complex delineation. This article reviews the literature on radiation of supra- and infraclavicular lymph nodes, with a special focus on technical aspects in delineation and its potential toxicity.

[Magnetic resonance imaging for delineation of prostate in radiotherapy: monocentric experience and review of literature]. / Imagerie par résonance magnétique et délinéation de la prostate en radiothérapie : expérience monocentrique et revue de la littérature.

PURPOSE: To assess the benefits of magnetic resonance imaging (MRI) in the dosimetric treatment planning for prostate radiotherapy. PATIENTS AND METHODS: Ten consecutive patients have been enrolled. They were treated for a low risk prostate adenocarcinoma. A rigid superimposition was performed between MRI and scan slides obtained at time of virtual simulation, then prostate volume was delineated by four to five physicians, on TDM slides and on MRI/TDM superimposition. For each treatment plan, we assessed the impact of MRI in terms of planned treatment volume (PTV) position, individual variability of prostate delineation and doses delivered to the critical organs. The prescribed dose was 74 Gy in 37 fractions to the PTV. RESULTS: PTV delineated on TDM (V(TDM)) were 1.15 (SD 3.71) larger than volumes delineated on MRI. Prostate apex was 4.6 mm (SD 2.87) lower on TDM than on MRI. Posterior limit of the prostate was in mean 4 mm more posterior on TDM. The variability between physicians in terms of prostate delineation was lower using MRI. For apex, these variations were 6.8 mm using TDM, versus 3.3 mm using MRI. Mean rectal dose was 8 % lower with MRI, compared to delineation using TDM. CONCLUSION: Superimposition TDM/MRI improves accuracy, decreases delineation variability, and allows to spare anterior part of the rectum from irradiation. It remains unknown whether this strategy translates into clinical benefit.

[Exclusive radiotherapy and concurrent endocrine therapy for the management of elderly breast cancer patients: case study and review of hypofractionated schemes]. / Hormonoradiothérapie exclusive dans la prise en charge du cancer du sein de la personne âgée : cas clinique et revue de la littérature des schémas hypofractionnés.

Normofractionated radiotherapy is standard for adjuvant management of patients treated with breast conservative surgery for breast cancer. However, many elderly patients are not eligible to such strategy, either because of concurrent diseases, or because the tumor is inoperable. Several protocols of exclusive radiotherapy have been reported in the literature, frequently using hypofractionated radiotherapy and endocrine therapy. We report a case of a patient treated with exclusive endocrine and radiotherapy and address the state of the art on hypofractionated schemes for the management of elderly breast cancer patients. While hypofractionated radiotherapy does not compromise the oncologic or cosmetic outcome, there is no prospective data that assesses the place of radiotherapy for the exclusive treatment of elderly patients. This strategy should be further assessed in clinical randomized trial.

[Benefit of a prolonged adjuvant treatment with temozolomide for the management of patients with glioblastoma]. / Intérêt d'un traitement d'entretien prolongé par témozolomide dans la prise en charge des patients atteints d'un glioblastome.

PURPOSE: Temozolomide has significantly improved the outcome of patients with glioblastoma. However, the optimal duration of continuation treatment after chemoradiation remains uncertain. This retrospective analysis aims at assessing the feasibility, the tolerance, and the potential benefit of prolonging adjuvant temozolomide more than six months, which is the reference protocol. PATIENTS AND METHODS: Forty-six patients were included in the analysis. Median age at diagnosis was 61 years old (range 40 to 77). Forty-five patients received a conformal external beam radiation with concurrent temozolomide-based chemotherapy. Then, 37 patients received adjuvant chemotherapy with temozolomide. The treatment was continued until progression or toxicity. RESULTS: During the adjuvant phase, no treatment discontinuation for toxicity was necessary. Eight patients required dose adaptation because of toxicity. Thirty-two patients presented tumor progression during the adjuvant phase. Overall median survival was 12.3 months (range 11-13.2 months) and progression-free survival (PFS) was 7.6 months (range 5.6-9.6 months). CONCLUSION: These results suggest feasibility of delivering temozolomide beyond the six months of the standard protocol, with mild toxicity and survival data at least comparable to those from literature. Prospective assessments are ongoing.

[Internal mammary chain irradiation in breast cancer: state of the art]. / Radiothérapie de la chaîne mammaire interne dans les cancers du sein: état des lieux.

Radiation therapy has a major role in the management of infiltrative breast cancers. However, there is no consensus for the prophylactic treatment of the internal mammary chain (IMC), with strategies that show strong differences according to centers and physicians. Indications for internal mammary chain radiotherapy are debated, since this treatment significantly increases the dose delivered to the heart and leads to potential technical difficulties. Important prospective data recently suggested that internal mammary chain radiotherapy would not be necessary, even in cases of internal or central tumor locations, or in patients with positive axillary lymph nodes. Although these data warrant confirmation by two other prospective trials, there is evidence that the indications for internal mammary chain radiotherapy should be careful and that high quality techniques should be used for decreasing the dose delivered to the heart. This review of literature presents the state of art on the radiotherapy of internal mammary chain, with special focus on the indications, techniques, and potential toxicity.

In vivo fluctuation of Tax, Foxp3, CTLA-4, and GITR mRNA expression in CD4+CD25+ T cells of patients with human T-lymphotropic virus type 1-associated myelopathy

HTLV-1 Tax expression exerts an inhibitory effect on the Foxp3 transcription factor in CD4+CD25+ T-regulatory cells (Treg). For a better understanding of the role of Tax mRNA in the gene expression of cellular markers we measured Tax, Foxp3, CTLA-4, GITR, TGF-β, and IL-10 mRNA in Treg cells of 50 patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP; 27 women and 23 men; mean age: 56.7 years). The control group consisted of 23 non-infected subjects (12 women and 11 men) with a mean age of 51.3 years. Real-time PCR was used to measure mRNA of Tax proteins and several cellular markers of Treg function. Determinations revealed a high level of Tax mRNA in HAM/TSP (124.35 copies/100 CD4+CD25+ T cells). Foxp3, GITR, and CTLA-4 mRNA levels were lower in HAM/TSP patients (mean ± SD, 22.07 ± 0.78, 9.63 ± 0.36, and 4.54 ± 0.39, respectively) than in non-infected controls (47.15 ± 12.94, 22.14 ± 1.91, and 21.07 ± 2.31). Both groups had similar levels of TGF-β and IL-10. An inverse relationship was found between Tax levels and Foxp3, CTLA-4, and GITR levels. Conversely, there was a direct correlation between levels of Foxp3, GITR, and CTLA-4. Disease severity and evolution time did not correlate with Tax or Foxp3 levels. The present results suggest that Tax and Foxp3 mRNA vary with the same degree of disease severity in HAM/TSP patients. Tax fluctuations may affect CTLA-4 and GITR expression via the Foxp3 pathway, causing virus-induced dysfunction of CD4+CD25+ T cells in HAM/TSP patients.

In vivo fluctuation of Tax, Foxp3, CTLA-4, and GITR mRNA expression in CD4(+)CD25(+) T cells of patients with human T-lymphotropic virus type 1-associated myelopathy.

HTLV-1 Tax expression exerts an inhibitory effect on the Foxp3 transcription factor in CD4(+)CD25(+) T-regulatory cells (Treg). For a better understanding of the role of Tax mRNA in the gene expression of cellular markers we measured Tax, Foxp3, CTLA-4, GITR, TGF-ß, and IL-10 mRNA in Treg cells of 50 patients with human T-lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP; 27 women and 23 men; mean age: 56.7 years). The control group consisted of 23 non-infected subjects (12 women and 11 men) with a mean age of 51.3 years. Real-time PCR was used to measure mRNA of Tax proteins and several cellular markers of Treg function. Determinations revealed a high level of Tax mRNA in HAM/TSP (124.35 copies/100 CD4(+)CD25(+) T cells). Foxp3, GITR, and CTLA-4 mRNA levels were lower in HAM/TSP patients (mean ± SD, 22.07 ± 0.78, 9.63 ± 0.36, and 4.54 ± 0.39, respectively) than in non-infected controls (47.15 ± 12.94, 22.14 ± 1.91, and 21.07 ± 2.31). Both groups had similar levels of TGF-ß and IL-10. An inverse relationship was found between Tax levels and Foxp3, CTLA-4, and GITR levels. Conversely, there was a direct correlation between levels of Foxp3, GITR, and CTLA-4. Disease severity and evolution time did not correlate with Tax or Foxp3 levels. The present results suggest that Tax and Foxp3 mRNA vary with the same degree of disease severity in HAM/TSP patients. Tax fluctuations may affect CTLA-4 and GITR expression via the Foxp3 pathway, causing virus-induced dysfunction of CD4(+)CD25(+) T cells in HAM/TSP patients.

Large hepatic mesenchymal hamartoma leading to mid-trimester fetal demise.

This report describes a fetus with a large multiloculated cystic liver mass. Two small abdominal cysts were seen on ultrasound at 19 weeks of gestation but the patient was referred to us at 23 weeks, after the mass had grown to 8.0 x 5.6 x 7.0 cm, displacing intra-abdominal organs, heart and diaphragm. There was a small amount of ascites but no hydrops. There was polyhydramnios and a thick hyperechoic placenta. After detailed sonograms and MRI suggested the diagnosis of cystic mesenchymal hamartoma of the liver, cyst decompression was favored and consent was obtained. Unfortunately, absence of fetal cardiac activity was noted on the day of the planned intervention. Autopsy confirmed the diagnosis and demonstrated placental changes consistent with mesenchymal stem villous hyperplasia of the placenta. Large fetal cystic abdominal masses that compress the heart, lungs and other organs may benefit from prenatal decompression. This is the first report of cystic hamartoma of the liver apparent on second-trimester sonography, and the fourth time such a lesion is associated with fetal or neonatal death out of 11 cases diagnosed prenatally.

Presence of HTLV-I Tax protein in cerebrospinal fluid from HAM/TSP patients.

Infection with human T-cell lymphotropic virus type I (HTLV-I) have been associated with the development of the HTLV-I-associated myelopathy/Tropical Spastic Paraparesis (HAM/TSP). The disease affects the pyramidal tract at the distal segments of spinal cord, generating a spastic paraparesis. We studied the presence of Tax protein in cerebrospinal fluid cells and spinal fluid (CSF) of 35 Chilean patients: 22 HAM/TSP patients (15 HTLV-I-seropositives, and 7 seronegatives), and 13 controls (9 PSP and 4 CJD non-infected patients). Tax antigens were evaluated with monoclonal antibodies reacting with Tax by immunofluorescence and ELISA assays in cerebrospinal fluid cells and CSF, respectively. Proviral was evaluated by PCR of tax gene in cerebrospinal fluid cells. Tax antigen was detected in CSF and lymphocytes of CSF from 4 and 12 HAM/TSP patients, respectively. Lymphocytes of CSF of 8 HAM/TSP (6 seropositives and 2 seronegatives) showed the presence of tax gene. These results show that cells of CSF from HAM/TSP patients are able to express and export Tax protein towards the CSF. This is the first report of the presence of Tax protein in cerebrospinal fluid cells and CSF from HAM/TSP HTLV-I seronegative patients.

Neonatal diabetes, with hypoplastic pancreas, intestinal atresia and gall bladder hypoplasia: search for the aetiology of a new autosomal recessive syndrome.

AIMS/HYPOTHESIS: Neonatal diabetes is a rare disease with several identified molecular aetiologies. Despite associations with other malformations, neonatal diabetes with intestinal and biliary anomalies has not been described. The current study aims to describe a new syndrome, and to examine a possible link with one of three genes known to cause neonatal diabetes. METHODS: Five clinical cases are described. Immunohistochemical staining for pancreatic islet hormones was performed on three of the infants. DNA from one infant was analysed for abnormalities of the PLAGL-1 (ZAC), glucokinase and PDX-1 (IPF-1) genes. RESULTS: Five infants (two sibling pairs from two families, and an isolated case) presented with neonatal diabetes, hypoplastic or annular pancreas, jejunal atresia, duodenal atresia and gall bladder aplasia or hypoaplasia. One sibling pair was born to consanguineous parents. One patient with a milder form is surviving free of insulin. Four children died in the first year of life despite aggressive medical management. Pancreatic immunohistochemistry revealed few scattered chromogranin-A-positive cell clusters but complete absence of insulin, glucagon and somatostatin. Exocrine histology was variable. In one case from the consanguineous family, molecular analysis showed no duplication or uniparental isodisomy of PLAGL-1 at 6q24, no contiguous gene deletion involving the glucokinase gene, and no mutation in the coding sequences or splice sites of PDX-1. CONCLUSIONS/INTERPRETATION: This combination of multiple congenital abnormalities has not been previously described and probably represents a new autosomal recessive syndrome involving a genetic abnormality that interferes with normal islet development and whose aetiology is as yet unknown.

In vitro cytoskeleton changes of mouse neurons induced by purified HTLV-1, and PBMC from HAM/TSP patients and HTLV-1 carriers.

HTLV-1 is the causative agent of HAM/TSP. This neurological disease affects the CNS producing damage of the motor tracts at the spinal cord. The HAM/TSP pathogenesis remains undefined. It could include direct and indirect actions of HTLV-1. We studied the effect of purified HTLV-1 and the PBMC of 22 Chilean patients co-cultivated with fetal neurons of mouse (CNh cells): 8 HAM/TSP, 8 HTLV-1 carriers, and 6 non-infected controls. The viral antigens and provirus in CNh cells was evaluated with monoclonal and polyclonal antibodies reacting with HTLV-1 by immunofluorescence assay and PCR at 0, 7 and 15 days of co-cultures, respectively. Viral antigens were detected in 0.1-0.5%, and 0-0.3% of the neurons incubated with lymphocytes of HAM/TSP patients and HTLV-1 carriers, respectively. Neurons incubated with cells of 7 HAM/TSP patients, and 3 HTLV-1 carriers showed the presence of nucleotide sequences of tax gene. These results would be showing that CNh cells would express viral antigens and provirus. The HTLV-1 or their proteins were capable in vitro to produce structural and growth changes in the cytoskeleton of CNh neurons. In this series, the purified HTLV-1 was more effective in the neural changes than PBMC of HAM/TSP or HTLV-1 carriers.

Extracellular matrix protein expression in cerebrospinal fluid from patients with tropical spastic paraparesis associated with HTLV-I and Creutzfeldt-Jakob disease.

The cerebrospinal fluid (CSF) is in direct contact with the extracellular space of the CNS, thus biochemical processes in the CNS could potentially be reflected in the CSF. Changes in extracellular matrix (ECM) proteins can be studied through their analysis in the CSF. ECM plays an essential role in CNS homeostasis and several proteins such as laminin (LN), fibronectin (FN), thrombospondin (TS) and heparan sulphate proteoglycan (HS, perlecan) form part of its structure. Possible changes in the levels of these proteins were investigated in two different pathologies--tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) (n=25) and Creutzfeldt-Jakob disease (CJD) (n=19)--and compared with those in a control group with or without neurological disease (n=25). CSF analyses were carried out using monoclonal or monospecific polyclonal antibodies. In comparison with the control group, it was found that TSP/HAM patients presented significantly higher levels of LN, TS and HS, while in CJD patients the levels of FN, TS and HS were increased. In CJD patients the HS level was almost double that of the TSP/HAM patients. These results suggest a distinct pattern of ECM proteins in CSF in relation to the type of neurological disease. TSP/HAM is a chronic motor disease that affects the white matter of the spinal cord, while CJD is a subacute dementia that affects cerebral neurons and their synapsis.

Matrix metalloproteinase profile in patients with Creuztfeldt-Jakob disease.

Preliminary findings suggest that abnormalities in matrix metalloproteinase (MMP) activity may be found in the cerebrospinal fluid (CSF) of patients with Creutzfeldt-Jakob disease (CJD). In this study of 16 subjects with CJD and 16 age-, and sex-matched controls, we determined the presence of MMP-2 and MMP-9 in their active and proenzyme forms, the relative levels of MMP-3 and four inhibitors of MMP activity (TIMP-1, TIMP-2, TIMP-3 and TIMP-4), and the concentration of 4-3-3 protein. The methodology used involved zymography and immunological techniques. The results indicate that, compared with controls, CJD patients have a significantly higher positive frequency of pro-MMP-9 and of the active form of MMP-2, along with significantly higher levels of TIMP-1 and TIMP-2, classical inhibitors of MMP-9 and MMP-2, respectively. We also found a positive correlation between 14-3-3 protein concentration and that of TIMP-1 and TIMP-2 levels (correlation coefficients of 0.793 and 0.798, respectively). These results suggest that abnormalities in MMP and TIMP profiles may be helpful in the biochemical characterisation of CJD.

Romboencefalitis: una forma de infección por Listeria monocytogenes en el sistema nervioso central / Rhomboencephalitis caused by listeria monocytogenes infection in the central nervous system

Listeria monocytogenes infections can involve the central nervous system in the form of a rhomboencephalitis. Three possible cases of rhomboencephalitis by Listeria monocytogenes are reported (2 females, aged 44 and 49 and a man of 36 years old). The three cases were preceded by an unspecific prodrome of headache, vertigo and fever in absence of a meningeal syndrome. The neurological stage was defined by the unilateral involvement of cranial nerves and the cerebellum and a clear inflammatory cerebrospinal fluid (CSF) with the presence of polymorphonuclear leukocytes, and normal glucose and protein levels. A magnetic nuclear resonance (MRI) showed the appearance of characteristic images, present in the bulboprotuberancial region. These images are one of the most constant features of this disease, reported in the literature. The early diagnosis of rhomboencephalitis was based on the clinical picture, the study of the CSF and the MRI, allowing the use of antimicrobials, prior to microbiological identification. Therefore, the risk of brain stem and cardiac complications of the disease is reduced.

Defective human T-cell lymphotropic virus type I (HTLV-I) provirus in seronegative tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM) patients.

Infection with human T-cell lymphotropic virus type I (HTLV-I) have been associated with the development of the tropical spastic paraparesis/HTLV-I-associated myelopathy (TSP/HAM). We studied the presence of HTLV-I provirus in peripheral blood mononuclear cells (PBMC) from 72 Chilean patients with progressive spastic paraparesis by polymerase chain reaction: 32 seropositive and 40 seronegative cases. We amplified different genomic regions of HTLV-I using primers of 5' ltr, tax, env/tax, pX, pol and env genes. These genes were detected from all seropositive patients. The seronegative patients were negative with 5' ltr, pol, env, and pX primers. However, amplified product of tax and env/tax genes was detected from 16 and four seronegative patients, respectively. Three of them were positive with both genetic regions. The results of this study show that the complete HTLV-I provirus is found in 100% of seropositive cases. In seronegative cases, clinically very similar of seropositive cases, was found only tax gene in 42.5% (17/40) of patients. These results suggest the presence of a defective HTLV-I provirus in some seronegative patients with progressive spastic paraparesis, and suggest a pathogenic role of this truncate provirus for a group of TSP/HAM.

Cambios neuropsicológicos y neurofisiológicos en la enfermedad de Fahr / Neuropsychological and neurophysiological features of Fahr's disease

BACKGROUND: Fahr's disease (basal ganglia calcification) is characterized by bi hemispherical calcium deposition in basal ganglia, dentate nucleus and semioval center. Its clinical manifestations are a rigid hypokinetic syndrome, mood disorders and cognitive impairment. AIM: To report to the results of a neurological assessment of three siblings with Fahr disease. PATIENTS AND METHODS: Three sisters, aged 55, 56 and 58 years, were studied. All had a rigid hypokinetic clinical picture associated with cerebellar involvement and a cognitive impairment that progressed in 8, 6 and 10 years respectively. Brain CAT scans showed symmetric and extensive calcifications of cerebellar white matter and dentate nuclei, pons, mesencephalon, lenticular nuclei, thalami and semioval centers. Hypoparathyroidism was ruled out. Cognition was assessed with WAIS and Benton tests and Weschler memory scale. The time of reaction to visual stimuli was studied. The processing speed of visual information and the interhemispheric conduction time of such information, were calculated. Cognitive evoked potentials (P 300) were also studied. RESULTS: Cognitive impairment involved verbal and visual-spatial memory, planning, attention and concentration capacities and visual constructive skills. There was a prolongation of reaction time latencies and loss of the normal asymmetry of interhemispheric transmission (without right to left facilitation). P 300 evoked potentials were absent. CONCLUSIONS: These observations suggest that the pathogenesis of cognitive and motor changes in Fahr's disease is based in a dysfunction of cortico basal connections and their interhemispheric relations. This defines a subcortical dementia secondary to mineral deposits in subcortical structures.

Comparative study of the epileptogenic effect of kainic acid injected into the cerebral cortex, hippocampus and amygdala in adult cats chronically implanted.

Intracerebral injection of kainic acid in cerebral cortex, hippocampus or amygdala in cats chronically implanted showed that: 1) Hippocampus and amygdala presented a greater sensitivity than the cerebral cortex, while hippocampus presented a greater sensitivity than the amygdala to the generation of an epileptic focus. 2) Comparison of latency, mean duration of afterdischarges, and the mean time period to obtain the peak intensity of the afterdischarge in the three cited structures, showed that mean latency of the first afterdischarge was significantly shorter in hippocampus and amygdala compared with the cerebral cortex. Moreover the mean time period to reach the peak intensity of the afterdischarge was again shorter in the subcortical structures. 3) The epileptic foci both in hippocampus and amygdala were blocked by CNQX and muscimol. 4) The behavioral changes depended on the intensity of the epileptic process. Tonic-clonic convulsions appeared only when the motor cerebral cortex was involved. Finally, 5) kainic acid injections in hippocampus and amygdala elicited an intense neuronal destruction and gliosis of these structures. We conclude that intracerebral injection of low doses of kainic acid in cats represent a good model to study focal epileptic thresholds in the CNS.

Induction and blockade of epileptic foci by intracerebral injection of glutamatergic agonists and antagonists in frerly moving cats.

The aim of the present work was to test in adult cats the capability of three glutamatergic agonists, NMDA, AMPA and ACDP as epileptogenic agents. Drugs were microinjected in amygdala or hippocampus, and once generated an epileptic focus three selective glutamatergic antagonists NMDA, CNQX and MCPG, were tested. Before and after injection both the EEG and the behavior were continuously monitored. The results were as follows: 1) AMPA showed a greater capability than NMDA or ACPD to generate a chronic epileptic focus; 2) AMPA elicited a greater epileptogenic effect in hippocampus than in amygdala; NMDA had similar epileptogenic effect in both cited structures, and ACPD had not effect; 3) of the three glutamatergic antagonists used to block a long lasting focus, the most effective one was CNQX, which showed a greater effect in hippocampus than in amygdala; 4) comparison between the epileptogenic effect of AMPA and kainic acid (first paper) in the same structure, showed that kainic acid is about 15 fold more epileptogenic. A discussion of the probable mechanisms of these results was undertaken.