Neurophysiological investigations of drug resistant epilepsy patients treated with vagus nerve stimulation to differentiate responders from non-responders.

BACKGROUND AND PURPOSE: In patients treated with vagus nerve stimulation (VNS) for drug resistant epilepsy (DRE), up to a third of patients will eventually not respond to the therapy. As VNS therapy requires surgery for device implantation, prediction of response prior to surgery is desirable. It is hypothesized that neurophysiological investigations related to the mechanisms of action of VNS may help to differentiate VNS responders from non-responders prior to the initiation of therapy. METHODS: In a prospective series of DRE patients, polysomnography, heart rate variability (HRV) and cognitive event related potentials were recorded. Polysomnography and HRV were repeated after 1 year of treatment with VNS. Polysomnography, HRV and cognitive event related potentials were compared between VNS responders (≥50% reduction in seizure frequency) and non-responders. RESULTS: Fifteen out of 30 patients became VNS responders after 1 year of VNS treatment. Prior to treatment with VNS, the amount of deep sleep (NREM 3), the HRV high frequency (HF) power and the P3b amplitude were significantly different in responders compared to non-responders (P = 0.007; P = 0.001; P = 0.03). CONCLUSION: Three neurophysiological parameters, NREM 3, HRV HF and P3b amplitude, were found to be significantly different in DRE patients who became responders to VNS treatment prior to initiation of their treatment with VNS. These non-invasive recordings may be used as characteristics for response in future studies and help avoid unsuccessful implantations. Mechanistically these findings may be related to changes in brain regions involved in the so-called vagal afferent network.

The turn of the gradient? Educational differences in breast cancer mortality in 18 European populations during the 2000s.

This study aims to investigate the association between educational level and breast cancer mortality in Europe in the 2000s. Unlike most other causes of death, breast cancer mortality tends to be positively related to education, with higher educated women showing higher mortality rates. Research has however shown that the association is changing from being positive over non-existent to negative in some countries. To investigate these patterns, data from national mortality registers and censuses were collected and harmonized for 18 European populations. The study population included all women aged 30-74. Age-standardized mortality rates, mortality rate ratios, and slope and relative indexes of inequality were computed by education. The population was stratified according to age (women aged 30-49 and women aged 50-74). The relation between educational level and breast cancer mortality was predominantly negative in women aged 30-49, mortality rates being lower among highly educated women and higher among low educated women, although few outcomes were statistically significant. Among women aged 50-74, the association was mostly positive and statistically significant in some populations. A comparison with earlier research in the 1990s revealed a changing pattern of breast cancer mortality. Positive educational differences that used to be significant in the 1990s were no longer significant in the 2000s, indicating that inequalities have decreased or disappeared. This evolution is in line with the "fundamental causes" theory which stipulates that whenever medical insights and treatment become available to combat a disease, a negative association with socio-economic position will arise, independently of the underlying risk factors.

Severe autonomic nervous system imbalance in Lennox-Gastaut syndrome patients demonstrated by heart rate variability recordings.

OBJECTIVE: Patients diagnosed with Lennox Gastaut syndrome (LGS), an epileptic encephalopathy characterized by usually drug resistant generalized and focal seizures, are often considered as candidates for vagus nerve stimulation (VNS). Recent research shows that heart rate variability (HRV) differs in epilepsy patients and is related to VNS treatment response. This study investigated pre-ictal HRV in generalized onset seizures of patients with LGS in correlation with their VNS response. METHODS: In drug resistant epilepsy (DRE) patients diagnosed with LGS video-electroencephalography recording was performed during their pre-surgical evaluation. Six HRV parameters (time and-, frequency domain, non-linear parameters) were evaluated for every seizure in epochs of 10 min at baseline (60 to 50 min before seizure onset) and pre-ictally (10 min prior to seizure onset). The results were correlated to VNS response after one year of VNS therapy. RESULTS: Seven patients and 31 seizures were included, two patients were classified as VNS responders (≥ 50 % seizure reduction). No difference in pre-ictal HRV parameters between VNS responders and VNS non-responders could be found, but high frequency (HF) power, reflecting the parasympathetic tone increased significantly in the pre-ictal epoch in both VNS responders and VNS non-responders (p = 0.017, p = 0.004). SIGNIFICANCE: In this pilot data pre-ictal HRV did not differ in VNS responders compared to VNS non-responders, but showed a significant increase in HF power - a parasympathetic overdrive - in both VNS responders and VNS non-responders. This sudden autonomic imbalance might have an influence on the cardiovascular system in the ictal period. Generalized tonic-clonic seizures are regarded as the main risk factor for SUDEP and severe seizure-induced autonomic imbalance may play a role in the pathophysiological pathway.

[Results of self-centering patellofemoral prosthesis: a retrospective study of 57 implants]. / Résultats de la prothèse fémoropatellaire autocentrique: à propos d'une série continue de 57 prothèses.

PURPOSE OF THE STUDY: The aim of this retrospective analysis was to report results obtained with a self-centering patellofemoral prosthesis. We wanted to determine whether self-centering still has indications for the treatment of patellofemoral osteoarthritis. MATERIAL AND METHODS: This was a continuous series of 57 knees operated on since 1986 in the same center for implantation of a self-centering patellofemoral prosthesis (Medinov then Depuy). Eight patients died and four were lost to follow-up. Two knees were excluded from the analysis after revision with a PFP. We report here the outcome of 43 prostheses at mean follow-up of six years two months (range 78 months to 15 years). The IKS score (200 points) and the ADL scale (in %) were recorded. The position of the prosthesis was assessed on plain X-rays. Mean age at implantation was 67.2 years. The main reasons for surgery were osteoarthritis secondary to dysplasia (60%) and primary disease (31.1%). RESULTS: At last follow-up, the IKS score was 157.2 points (range 76-195). The mean ADL score was 74.1/100 (48.8-96.3). The IKS evaluation showed good outcome in 66.7% of knees. The ADL scale gave a less satisfactory outcome: 57.7% good outcome for this scale which takes into account all knee functions for activities of daily life. Outcome was better among patients with trochlear dysplasia. Eleven patients (24.4%) had had revision surgery for total knee arthroplasty. Preoperatively, the trochlear angle was smaller in revision cases (p=0.023). In these patients, the first prosthesis was more anterior (p=0.004) with a greater horizontal axis (p=0.015). DISCUSSION: Our outcomes were less satisfactory than the average results in the literature. It must be noted however, that the concept of a good outcome depends on the scale used for assessment. We found in our series a 10% difference between the ADL scale and the IKS score. Independently of the assessment scale used, outcome was better in knees with osteoarthritis secondary to dysplasia. An analysis of the X-ray findings disclosed technical errors leading to failure. The outcome of patellofemoral prosthesis depends essentially on two factors: technical precision and patient selection. CONCLUSION: In light of these findings, we have come to limit still further the rare indications for patellofemoral prostheses. The typical indication is isolated advanced patellofemoral osteoarthritis secondary to patellofemoral dysplasia unresponsive to medical treatment in patients aged 50-70 years. Revision with a total knee arthroplasty required changing the patellar insert if worn. We have not had any particular problem with revision total knee arthroplasty after patellofemoral prosthesis.

[Analysis of meniscal lesions accompanying anterior cruciate ligament tears: A retrospective analysis of 156 patients]. / Lésions méniscales constatées lors de la reconstruction du ligament croisé antérieur: siège et nature dans une série continue de 156 patients.

PURPOSE OF THE STUDY: The purpose of this retrospective study of a continuous series was to document preferential types and localizations of meniscal lesions accompanying anterior cruciate ligament tears and to demonstrate the relationships between meniscal lesions, patient age and time from trauma to surgery. MATERIAL AND METHODS: One hundred fifty-six patients with no history of meniscal lesions underwent ligamentoplasty in 2003. All procedures were performed by the same operator. The time from trauma to surgery was 31.6 months on average. This was a retrospective continuous series using data from detailed operative reports. RESULTS: An isolated lesion of the medial meniscus was observed in 25.6% of cases. There was an isolated lesion of the lateral meniscus in 21.8% and lesions of both menisci in 9%. The most frequent injury was a longitudinal fissuration, for both menisci. Patient age and time from trauma to surgery were statistically correlated with presence of a medial lesion. There was no statistical relationship for the lateral meniscus nor for type of meniscal injury. DISCUSSION: The proportion of lesions to the lateral meniscus appeared to be unaffected by age or time to surgery after trauma, suggesting that lateral meniscal lesions occurred at the time of the initial curciate injury. On the contrary, the incidence of medial lesions increased with time and patient age, confirming the important role of the medial meniscus to block anterior displacement of the knee. We thus recommend early repair of anterior cruciate ligament tears in order to avoid medial meniscectomy which would increase with increasing time from injury to surgery and thus affect the postoperative outcome.

The systemic kainic acid rat model of temporal lobe epilepsy: Long-term EEG monitoring.

Animal models reproducing the characteristics of human epilepsy are essential for the elucidation of the pathophysiological mechanisms. In epilepsy research there is ongoing debate on whether the epileptogenic process is a continuous process rather than a step function. The aim of this study was to assess progression of epileptogenesis over the long term and to evaluate possible correlations between SE duration and severity with the disease progression in the kainic acid model. Rats received repeated KA injections (5mg/kg) until a self-sustained SE was elicited. Continuous depth EEG recording started before KA injection and continued for 30 weeks. Mean seizure rate progression could be expressed as a sigmoid function and increased from 1 ± 0.2 seizures per day during the second week after SE to 24.4 ± 6.4 seizures per day during week 30. Seizure rate progressed to a plateau phase 122 ± 9 days after SE. However, the individual seizure rate during this plateau phase varied between 14.5 seizures and 48.6 seizures per day. A circadian rhythm in seizure occurrence was observed in all rats. Histological characterization of damage to the dentate gyrus in the KA treated rats confirmed the presence of astrogliosis and aberrant mossy fiber sprouting in the dentate gyrus. This long-term EEG monitoring study confirms that epileptogenesis is a continuous process rather than a step function.

Socioeconomic inequalities in mortality among elderly people in 11 European populations.

STUDY OBJECTIVE: To describe mortality inequalities related to education and housing tenure in 11 European populations and to describe the age pattern of relative and absolute socioeconomic inequalities in mortality in the elderly European population. DESIGN AND METHODS: Data from mortality registries linked with population census data of 11 countries and regions of Europe were acquired for the beginning of the 1990s. Indicators of socioeconomic status were educational level and housing tenure. The study determined mortality rate ratios, relative indices of inequality (RII), and mortality rate differences. The age range was 30 to 90+ years. Analyses were performed on the pooled European data, including all populations, and on the data of populations separately. Data were included from Finland, Norway, Denmark, England and Wales, Belgium, France, Austria, Switzerland, Barcelona, Madrid, and Turin. MAIN RESULTS: In Europe (populations pooled) relative inequalities in mortality decreased with increasing age, but persisted. Absolute educational mortality differences increased until the ages 90+. In some of the populations, relative inequalities among older women were as large as those among middle aged women. The decline of relative educational inequalities was largest in Norway (men and women) and Austria (men). Relative educational inequalities did not decrease, or hardly decreased with age in England and Wales (men), Belgium, Switzerland, Austria, and Turin (women). CONCLUSIONS: Socioeconomic inequalities in mortality among older men and women were found to persist in each country, sometimes of similar magnitude as those among the middle aged. Mortality inequalities among older populations are an important public health problem in Europe.

Marriages and fertility among Turkish and Moroccan women in Belgium: results from census data.

The patterns of family formation and fertility behavior of Turkish and Moroccan women in Belgium are changing rapidly. The census data (1991) indicate a fertility decline. The reasons are changes in the nuptiality patterns, contraceptive behavior, and migratory flows. The changes are not identical in both communities. Young cohorts postpone their marriage, but this is most prominent among Moroccan women. On the other hand, young Turkish women have a clear preference for smaller families. The changes also differentiate according to migrant "generation" and level of education. The changes are not restricted to Belgium but are also observed in the countries of origin.

Socioeconomic status and ischaemic heart disease mortality in 10 western European populations during the 1990s.

OBJECTIVE: To assess the association between socioeconomic status and ischaemic heart disease (IHD) mortality in 10 western European populations during the 1990s. DESIGN: Longitudinal study. SETTING: 10 European populations (95,009,822 person years). METHODS: Longitudinal data on IHD mortality by educational level were obtained from registries in Finland, Norway, Denmark, England/Wales, Belgium, Switzerland, Austria, Turin (Italy), Barcelona (Spain), and Madrid (Spain). Age standardised rates and rate ratios (RRs) of IHD mortality by educational level were calculated by using Poisson regression. RESULTS: IHD mortality was higher in those with a lower socioeconomic status than in those with a higher socioeconomic status among men aged 30-59 (RR 1.55, 95% confidence interval (CI) 1.51 to 1.60) and 60 years and over (RR 1.22, 95% CI 1.21 to 1.24), and among women aged 30-59 (RR 2.13, 95% CI 1.98 to 2.29) and 60 years and over (RR 1.36, 95% CI 1.33 to 1.38). Socioeconomic disparities in IHD mortality were larger in the Scandinavian countries and England/Wales, of moderate size in Belgium, Switzerland, and Austria, and smaller in southern European populations among men and younger women (p < 0.0001). For elderly women the north-south gradient was smaller and there was less variation between populations. No socioeconomic disparities in IHD mortality existed among elderly men in southern Europe. CONCLUSIONS: Socioeconomic disparities in IHD mortality were larger in northern than in southern European populations during the 1990s. This partly reflects the pattern of socioeconomic disparities in cardiovascular risk factors in Europe. Population wide strategies to reduce risk factor prevalence combined with interventions targeted at the lower socioeconomic groups can contribute to reduce IHD mortality in Europe.

Education level inequalities and transportation injury mortality in the middle aged and elderly in European settings.

OBJECTIVE: To study the differential distribution of transportation injury mortality by educational level in nine European settings, among people older than 30 years, during the 1990s. METHODS: Deaths of men and women older than 30 years from transportation injuries were studied. Rate differences and rate ratios (RR) between high and low educational level rates were obtained. RESULTS: Among men, those of low educational level had higher death rates in all settings, a pattern that was maintained in the different settings; no inequalities were found among women. Among men, in all the settings, the RR was higher in the 30-49 age group (RR 1.46, 95% CI 1.32 to 1.61) than in the age groups 50-69 and > or = 70 years, a pattern that was maintained in the different settings. For women for all the settings together, no differences were found among educational levels in the three age groups. In the different settings, only three had a high RR in the youngest age group, Finland (RR 1.33, 95% CI 1.01 to 1.74), Belgium (RR 1.38; 95% CI 1.13 to 1.67), and Austria (RR 1.49, 95% CI 0.75 to 2.96). CONCLUSION: This study provides new evidence on the importance of socioeconomic inequalities in transportation injury mortality across Europe. This applies to men, but not to women. Greater attention should be placed on opportunities to select intervention strategies tailored to tackle socioeconomic inequalities in transportation injuries.

Socio-economic inequalities in health expectancy in Belgium.

Various international studies have demonstrated socio-economic differences in health. Linking the 1991 Census to the National Register and using the Health Interview Survey 1997 has enabled assessment of the association between the level of education and health in Belgium using the composite indicator 'health expectancy'. The Sullivan method was used to calculate health expectancy on the basis of current probability of death and prevalence of perceived health. Two measures of educational attainment were used: absolute educational attainment and the position on a relative hierarchical educational scale obtained by a regression-based method. The latter measure enables international comparisons. Differences in health expectancy by education were spread over the whole range of the educational hierarchy, and were consistently larger among females than males. At 25 years of age, the difference in health expectancy between different levels of education reached up to 17.8 and 24.7 years in males and females, respectively. Compared with people with the highest educational attainment, males and females at the lowest level of education spent more than 10 and 20 additional years in poor perceived health, respectively. Between ages 25 and 75 years, the difference in health expectancy between people with the lowest and highest levels of education was 17 years among males and 21 years among females. Compared with people at the top of the relative educational scale, males and females at the bottom of the scale had 13.6 and 19.7 additional years in poor perceived health, respectively. The conclusions of this study in Belgium are consistent with studies in other countries. People with a low level of education have shorter lives than people with a higher level of education. They also have fewer years in good perceived health, and can expect more years in poor health in their shorter lives. The inequality in health expectancy seems to be greater in females than males.