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Can we predict refractory epilepsy at the time of diagnosis?

The early prediction of intractability is a major challenge in epileptology. Some prognostic factors have been pointed out, most of which simply underlined that partial epilepsy is more difficult to control than idiopathic generalized epilepsy (IGE). Indeed, the main predictors are the presence of a brain lesion demonstrated by neuroimaging or suggested by a neurological deficit or a developmental delay, as well as electroclinical evidence of non idiopathic partial epilepsy. Little is known about the relationship between the location of the epileptogenic area and the chance of being seizure-free in patients with partial epilepsy. Some data suggest that temporal lobe epilepsy (TLE) is more difficult to control than other partial epilepsies, but this might only reflect the prognostic impact of hippocampal sclerosis. Indeed, several studies have shown that the majority of patients with MRI evidence of hippocampal sclerosis develop refractory epilepsy. This observation also applies to patients with malformation of cortical development (MCD). The response to the first AED is another early predictor of refractory epilepsy. At the time of diagnosis, several prognostic factors are available to predict drug resistance, but further studies are still needed to better delineate the specific role of each of these factors, and to offer a more accurate prediction of long term seizure outcome.

Drug Resistance↗

The impact of epilepsy surgery on mortality.

Patients with refractory epilepsy suffer from an increased risk of death, primarily due to seizure-related fatalities including sudden unexpected death (SUDEP), which could be conceivably avoided by surgical cure of the epilepsy. Several series have addressed this issue by comparing the mortality rate between medically and surgically treated drug resistant populations, as well as between patients, seizure free and non seizure free post-operatively. Results from some studies suggest that successful temporal lobe surgery reduced the risk of death to that observed in the normal population, whereas patients who continue to suffer recurrent seizures still present an increased standardized mortality ratio (SMR). However, other series have failed to replicate this finding, or found no difference in the overall mortality and SUDEP rates between operated and medically treated patients. All the above studies suffer various types of methodological limitations, hampering any definite conclusion regarding the impact of epilepsy surgery on mortality. However, part of the apparently discordant reported findings might be reconciled through the following framework. Patients who will eventually respond favourably or unfavourably to an anterior temporal lobectomy might already differ in the risk of seizure-related death, pre-operatively. Specifically, patients whose temporal lobe epileptogenic network extends to the perisylvian region (temporal plus epilepsy) appear to be at higher risk of failed TLE surgery, secondary generalised tonic-clonic seizures, ictal apnoea or insula-driven severe cardiac arrhytmias. This population might carry most of the SUDEP burden, both pre- and post-operatively, accounting for the lack of an obvious net reduction of seizure related deaths after temporal lobe surgery. A multicentric study has recently been launched in order to test this hypothesis, and will hopefully help to conclude on the impact of epilepsy surgery on mortality outcome.

Cause of Death↗

Quality of life after successful epilepsy surgery: evaluation by occupational achievement and income acquisition.

OBJECTIVES: A comprehensive epilepsy surgery program has been developed at Chulalongkorn University Hospital, Thailand to reach an international standard level, rendering patients good surgical outcomes comparable to developed countries. After successful operation, seizure free patients have become independent, self earning or employed. However, quality of life (QOL) in terms of occupational achievement and income acquisition after epilepsy surgery has never been studied. These indicators reflect the ultimate QOL in the aspects of actual independency, intact brain functions, mental health and psycho-social interactions. The authors therefore conduct the study on improvement of QOL after successful epilepsy surgery using these parameters. MATERIAL AND METHOD: One hundred and eleven intractable epilepsy who have become seizure free to worthwhile improved (Engel class I to III) after standard presurgical evaluation and epilepsy surgery from January 2002 to December 2004 were evaluated. The patients were followed up for 3 years. The occupational status and incomes were categorized according to the ranking of the patients' functioning levels. The pre and post surgery work abilities, employment and incomes were interviewed and compared. Mc Nemar test and paired t-test were used for statistical analyses. RESULTS: The average age of the 111 adults (54 males and 57 females) was 33.7 +/- 9.2 years. Eighty two percent of the patients had temporal lobe epilepsy (TLE) with mesial temporal sclerosis (MTS) and underwent standard anterior temporal lobectomy. The rest had tumors, cortical dysplasia or scar and received lesionectomy or cortical resection assisted by intra-operative or intra-cranial EEG. The overall seizure free rate is 83.8%. The occupational status of the subjects was shown to improve significantly after surgery from unemployed to higher categories of professional achievement (p < 0.001). The number of unemployed and no income individuals decreased from 66 to 25 cases (62.1% reduction rate) after surgery (p < 0. 001). Reciprocally, the number of persons who achieved professional jobs with regular incomes or salaries increase from 30 to 53 cases (43.4% increasing rate) (p < 0.001). The patients who have not acquired any income increment showed improvement in working ability after epilepsy surgery. The average annual incomes per capita shows the increasing rate of 45.08%, from 55,657.85 Baht (approximately U.S. dollars 1390) to 80,748.15 Baht (approximately U.S. dollars 2018), with strong statistical significance (p < 0.001). The improvement is best seen in seizure free than in non-seizure free subjects. CONCLUSION: The present study, to the authors 'knowledge, is the first to use work abilities, professional achievement and income acquisition to assess the ultimate QOL after epilepsy surgery. Most subjects have been shown to significantly improve their postoperative lives in terms of occupational accomplishment and income increment, especially in seizure free individuals. The need for expansion of epilepsy surgery is emphasized.

Achievement↗

Surgery in temporal lobe epilepsy patients without cranial MRI lateralization.

High resolution MRI is very important in the evaluations of patients with intractable temporal lobe epilepsy in preoperative investigations. Morphologic abnormalities on cranial MRI usually indicate the epileptogenic focus. Intractable TLE patients who have normal cranial MRI or bilateral hippocampal atrophy may have a chance for surgery if a certain epileptogenic focus is determined. We evaluated the patients who were monitorized in Gazi University Medical Faculty Epilepsy Center from October 1997 to April 2004. Seventy three patients, who had a temporal epileptogenic focus, underwent anterior temporal lobectomy at Ankara University Medical Faculty Department of Neurosurgery. Twelve of them (16, 4%), did not have any localizing structural lesion on cranial MRI. Of the 12 patients examined 6 had normal findings and 6 had bilateral hippocampal atrophy. Of these 12 patients, 6 (50%) were women and 6 (50%) were men. The ages of patients ranged from 7 to 37 (mean: 24.5). Preoperatively long-term scalp video-EEG monitoring, cranial MRI, neuropsychological tests, and Wada test were applied in all patients. Five patients, whose investigations resulted in conflicting data, underwent invasive monitoring by the use of subdural strips. The seizure outcome of patients were classified according to Engel with postsurgical follow-up ranging from 11 to 52 (median: 35.7) months. Nine patients (75%) were classified into Engel's Class I and the other 3 patients (25%) were placed into Engel's Class II. One patient who was classified into Engel's Class II had additional psychiatric problems. The other patient had two different epileptogenic foci independent from each other in her ictal EEG. One of them localized in the right anterior temporal area, the other was in the right frontal lobe. She was classified in Engel's Class II and had no seizure originating from temporal epileptic focus, but few seizures originating from the frontal region continued after the surgery. In conclusion, surgery was successful in all 12 patients. We think that patients with no MRI lateralizing or localizing lesion should undergo epilepsy surgery after detailed presurgical evaluations, including invasive monitoring.

Adolescent↗

[4-Tesla 1H MR spectroscopy in patients with temporal lobe epilepsy].

7 patients with drug-resistant temporal lobe epilepsy (TLE) and localized EEG-focus were investigated with a 4 Tesla whole body MR-scanner. Proton (1H) magnetic resonance (MR) spectra were analyzed quantitatively and compared to the healthy side. MRS allowed the differentiation of the following metabolites in 5 patients: N-acetyl-aspartate (NAA), creatine and phosphocreatine, phosphorylcholine and glycerophosphorylcholine, beta- and gamma-glutamate (GLU). To compare the results with those of an already evaluated normal population, these metabolites were measured also in parietal region. The standard deviation was 42-46% in the patients. Unfortunately, in the temporal region, the field homogeneity was worse than parietal and thus the spectral analysis less distinct especially for GLU with a standard deviation of 45% for NAA and 66% for GLU on the healthy side. Thus, no significant findings were seen on focus side. There was only a tendency to an elevation of glutamate and a reduction of N-acetyl-aspartate.

Adolescent↗

[Scale for tobacco evaluation in different countries].

Tobacco causes worldwide over five millions of death, in 2050 it is expected to die over five hundred millions, in the Czech Republic eighteen thousand people die for diseases related to tobacco, in average 15 years earlier then no smokers. Systematic tobacco control is therefore necessary both in individual countries and worldwide. Tle desribed scale serves to its comparison in different countries.

Europe↗

Immunological comparison of constitutive beta-lactamases of gram-negative bacteria by neutralization in zymogram gels: properties of anti-TEM-1 and anti-TEM-2 sera.

The zymogram technique was applied to a beta-lactamase neutralization assay with anti-TEM-1 and anti-TEM-2 sera. Both were shown to contain neutralizing antibodies directed towards various beta-lactamases of Gram-negative bacteria. The quantitative neutralization allowed classification into five groups of the 28 beta-lactamases used as standards and 61 from clinical isolates. In the first were enzymes such as TEM-1 and TEM-2 including TLE-1, SHV-1, SHV-2, penicillinases of Klebsiella pneumoniae and CTX-1. Partial neutralization distinguished two groups containing the CARB group of enzymes, which are different from PSE-2 and PSE-3, and the MAL penicillinases of Levinea malonatica, which are different from L. amalonatica enzymes. Broad spectrum beta-lactamases of K. oxytoca constituted a unique group of partially neutralized enzymes. Among the beta-lactamases not neutralized by either serum were the plasmid-mediated OXA-enzymes, various species-specific beta-lactamases and cephalosporinases. The antigenic similarities of the enzymes appeared to correlate with the extent of similarities of their catalytic properties, namely those of penicillinases. Such comparisons between the beta-lactamase groups provide an indirect approach to the physiological and structural analysis of established and recently evolved beta-lactamases.

Epitopes↗

[Infiltrating transitional carcinoma of the bladder. Is the P/T ratio a reliable index to evaluate the effectiveness of preoperative radiotherapy on tumors of the bladder?].

To determine the efficacy of preoperative radiotherapy, we used the following index: change in the clinical relative to the pathological state. We analyzed the series of our department, which was comprised of 175 patients who had undergone radical cystectomy. The P/T ratio was obtained in 138; it dropped in 26 (19%), remained unchanged in 57 (41.3%), and increased in 55 (40%). Analysis of the disease-free interval and survival by Kaplan and Meier's method showed a significantly higher difference for the patient groups with tumor Po + P less than T and P = T than for those with P greater than T, and there were no significant differences between the Po + P less than T and P = T patient groups. However, analysis of the TLE and survival curves for group P = T by comparing the three treatment regimens utilized showed no evidence that preoperative radiotherapy prolongs both parameters. The same finding was observed for the group whose P was greater than T. Evidently, prognosis is good for the group whose P dropped. However, we do not believe that it is ascribably to the beneficial effects of radiotherapy on the tumor. We believe that this is mainly due to the fact that, by definition, patients with more aggressive tumors are excluded. In our series, P3 and P4 tumors are classed under the groups whose P is "equal to" or "greater than".

Carcinoma, Transitional Cell↗

[Lympho-epithelial thymoma. Anatomo-clinical and therapeutic study of 113 cases].

One hundred and thirteen cases of lympho-epithelial thymomas were studied retrospectively: 56 were of epithelial type, 20 of lymphocytic type, 30 were mixed and 7 were not defined. Eighty-eight were operated on (20 stages I, 47 stages II, 13 stages III and 8 stages IV). There were 69 primary resections (57 complete and 12 incomplete), followed by radiotherapy in 54 cases and 19 secondary resections after radiotherapy (10 complete and 19 incomplete). Twenty-five patients did not have an operation and were treated with radio- and chemotherapy. After primary resection the actuarial survival at 5 years was 64.07% and at 10 years 50.86%. After a secondary resection it was 43.74% at 5 years. After radiotherapy it was 18.67% at 5 years. In operated cases the prognostic importance of staging was confirmed. The cytological structure was not. In myasthenic cases the secondary respiratory complications worsened the prognosis. Post-operative radiotherapy seems to be justified in all cases, but its effect is not statistically significant when resection was complete. Those operated after radiotherapy only showed a benefit if the resection was complete. The outcome of metastatic disease in TLE has been under-estimated and seems to depend on local control of the tumour. The use of chemotherapy remains to be defined.

Adolescent↗

Enterotoxigenic E. coli in humans.

E. coli strains isolated from persons having diarrhoeal disease were tested for the production of TS enterotoxin. The production of TSE was demonstrated in 2.5% in a series of 80 strains isolated from children under one year of age, having acute diarrhoea. TSE was produced by 8.4% of E. coli strains out of 59 strains isolated from patients over one year of age. Among these strains, an interesting E. coli strain was isolated from the patient T. J., which produced TSE for more than 15 months. The production of TLE was tested though not proved in all strains by experiment on an isolated intestinal loop of an adult rabbit. The test on suckling mice so far appears to be the most suitable test for the demonstration of TSE. The results were considered positive when the index (the ratio of the weight of the whole intestine to the weight of the rest of the body) was higher than 0.08 while indices up to 0.078 were considered negative. E. coli strains with indices of intermediate values and strains with temporary production of TSE, occurring particularly in very small children, deserve special attention. The height of the indices was not influenced by a 30-minute exposure at 60 degrees C, but a decrease in the values of the indices was observed after boiling for a period of 15 min. The occurrence of E. coli strains producing TSE is evidently small in humans in European countries but, without doubt, they are important in the aetiology of diarrhoeal diseases.

Animals↗

[Use of stationary-growth broth cultures for obtaining Escherichia enterotoxins. II. Study of Escherichia preparations isolated from diarrhea patients].

The preparation, simple in manufacture and consisting of the supernatant fluid (SF) of 48-hour cultures grown in flasks with Hottinger's broth without shaking, was shown to be suitable for the detection of enterotoxigenic E. coli (ETEC) in diarrhea patients. SF of the cultures of 1206 E. coli strains isolated from 809 adults, together with control preparations, were studied by means of anal test in suckling mice, used to detect thermostable enterotoxin (TSE), and the paw edema test, used to detect thermolabile enterotoxin (TLE). These SF contained highly active TSE and having specific action. The use of SF ensured the high frequency of ETEC detection in patients with different intestinal diseases (in 262 out of 430 patients), placed in the same hospital. The specificity of these results and the relation of the isolated ETEC to the diseases diagnosed in the patients were confirmed by the fact that the frequency of ETEC detection was significantly less in healthy persons (in 22 out of 242 subjects).

Adult↗

[Memory disorders in epileptic patients. A study of pre-postsurgical follow-up].

In general terms, epileptic patients with temporal lobe epilepsy (TLE) show mnesic deficits. In the case of medically intractable epilepsy (around 20%) the neurosurgery intervention is a widely accepted treatment. The cognitive effects of surgery have been reported in last years; they emphasize the mnesic positive changes of contralateral area. In the same sense they have reported a negative change on mnesic modality in ipsilateral area. This paper present a study in which the mnesic deficits of twenty eight pharmaco resistant epileptic patients have been evaluated and followed up. These patients have been submittes to a surgical treatment at the Epilepsy Surgical Unit of the Hospital de La Princesa (Madrid). The assessment pre and postoperative tested six months apart. The most common cognitive deficit affect bimodally to mnesic functions: so in the verbal as in the visospatial modality. This deficit correlated with the years epilepsy. Meanwhile, the following up study indicates that a relevant numbers of these patients show an improvement in the function of the contralateral hemisphere with respect to the area surgically treated. This finding probably is the consequence of seizure free.

Adolescent↗

Magnetic resonance imaging in symptomatic/cryptogenic partial epilepsies of infants and children.

In order to identify the brain lesions of symptomatic/cryptogenic partial epilepsies (S/CPEs) in infants and children, magnetic resonance imaging (MRI) studies, thorough encephalographic (EEGic) studies, and detailed clinical and neurologic evaluations were obtained in 300 infants and children who were diagnosed to have S/CPEs with onset before the age of 13 years during the past 7 years. The overall detection rate of brain lesions by MRI was 41.7% (125/300). Congenital malformations (18 cases), vascular malformations (9 cases), neurocutaneous syndromes (13 cases), and space-taking lesions (20 cases) constitute a large percentage of SPEs in infants and children. A variety of insults such as infection, ischemia, hemorrhage, trauma and metabolic disorders can result in destructive parenchymal loss lesions including porencephaly, focal atrophy, hemiatrophy, and diffuse brain atrophy (20 cases). Major etiologic factors leading to infarction, encephalomalacia, leukomalacia, included trauma, hvpoxicischemic encephalopathy (HIE), systemic lupus erythematosus (SLE), encephalitis, vasculitis, venous thrombosis, vasculopathies, and heart problems (22 cases). Mesial temporal sclerosis (MTS) could be evidenced in around 20% (18/95) of cases with temporal lobe epilepsy (TLE), which was strongly associated with past histories of febrile seizures and encephalitis complicated by status epileptics. However, cases with porencephaly, global atrophy or delayed myelination of unilateral temporal lobe on MRI were more related to HIE. With the advent of neuroimaging techniques, particularly MRI, a wide variety of underlying pathology can be detected as a cause of symptomatic partial epilepsies in pediatric patients. The occurrence of S/CPE indicates the presence of localized brain dysfunction, and many of the causes are potentially treatable. An orderly and thorough clinical and laboratory investigations, as well as neuroimaging studies should be made to diagnose and treat any underlying conditions.

Adolescent↗