Preventing Teratogenicity in Women with Epilepsy.

Over the last 50 years there has been a significant increase in our understanding of the issues faced by women with epilepsy, in both planning and undertaking pregnancy. The risks of teratogenicity associated with antiseizure medications have emerged slowly. The major pregnancy registers have substantially contributed to our knowledge about teratogenic risk associated with the commonly used antiseizure medications. However, there are substantial gaps in our knowledge about the potential risks associated with many third-generation drugs. The remit of the pregnancy registers and the wider research focus has moved beyond anatomical major congenital malformations. Increasingly neurodevelopmental and behavioral abnormalities have been investigated after in utero exposure to antiseizure medications. Public health approaches can help reduce the risk of teratogenicity. However, neurologists still have a vital role in reducing the risk of teratogenicity at an individual level for women attending their clinic. They also have responsibility to ensure that women with epilepsy are aware of the rationale for the different available options.

Investigative practice into sudden death in epilepsy: A global survey.

OBJECTIVES: Sudden death is a recognized consequence of epilepsy. Little is known about the practice of confirming the cause of sudden death from most nations. We sought to determine how often autopsy is undertaken, clinician confidence in cause of death and identify the factors which may influence autopsy utilization. MATERIALS & METHODS: An online questionnaire survey was sent to all International League Against Epilepsy (ILAE) chapters chairpersons, asking them to complete the survey based on their perceptions in their country. Questions included: confidence in cause of death in people with epilepsy, frequency of autopsy uptake, and perceived barriers to an accurate diagnosis and ongoing research work. Data were analyzed by chi-squared, Kruskal-Wallis and Spearman rank analysis. RESULTS: Responses were obtained from 77 of 114 individual chapter leaders (68%). Legal, coronial, family attitudes, including cultural and religious factors, to autopsy were considered the major barriers to obtaining an accurate diagnosis. Only 13% had a high level of confidence in the accuracy of the cause of death. There was greater confidence in the diagnosis of the causes of sudden death in epilepsy in the countries with higher autopsy rates. Sixty-six percent of responders were not aware of published or unpublished research or audits on sudden death in epilepsy in their country in the last decade. CONCLUSIONS: Significant disparities exist in the investigation of sudden death in epilepsy across countries and identified factors in this study provide an opportunity to formulate a global public health strategy to help overcome this gap.

Online behavior of people visiting a scientific website on epilepsy.

We investigated the online behavior of Internet users consulting the website of the Italian Chapter of the International League Against Epilepsy (Lega Italiana Contro l'Epilessia [LICE]). We obtained the visualization statistics of the LICE website using AWStats (https://awstats.sourceforge.io/) and Google Trends (https://trends.google.com/trends/), and compared the statistics of years 2010, 2014, and 2017. The following variables were analyzed: number of unique visitors and visits, visit duration, the day of week and rush hours, most downloaded documents, most viewed pages, keyphrases and keywords used for online searches, origins of searches, and geographic trends of Google searches related to the LICE. The total numbers of unique visitors, visits and page views remained quite stable over time. Most visits (70 to 76.7%) lasted less than 30 s. The most frequent keyphrases and keywords used for online searches were related to clinical guidelines and driving license. Among the most frequently downloaded documents were general guides on epilepsy. The pages with the list of epilepsy centers endorsed by the LICE and those with the list of LICE guidelines were among those most frequently viewed, together with educational videos. Most users directly accessed the website without being referred from external links. No information on geographic origin of Google searches was available. The visualization statistics suggested two distinct populations of visitors. The first one is likely represented by physicians who seek specialist information on diagnosis and management of epilepsy, including guidelines. The second population is represented by lay people who seek accessible and easily comprehensible information to better understand epilepsy and know which centers are best for its management.

Changing antiepilepsy drug-prescribing trends in women with epilepsy in the UK and Ireland and the impact on major congenital malformations.

OBJECTIVES: After 20 years of data collection, pregnancy registers have informed prescribing practice. Various populations show trends for a reduction in valproate prescribing, which is associated with an increased risk of anatomical teratogenesis and neurodevelopmental effects in those exposed in utero. Our aim was to determine if any shifts in prescribing trends have occurred in the UK and Ireland Epilepsy and Pregnancy Register cohort and to assess if there had been any change in the overall major congenital malformation (MCM) rate over time. METHODS: The UK and Ireland Epilepsy and Pregnancy Register, a prospective, observational, registration and follow-up study established in 1996, was used to determine the changes in antiepileptic drugs (AEDs) utilised during pregnancy and the MCM rate between 1996 and 2016. Linear regression analysis was used to assess changes in AED utilisation, and Poisson regression was used for the analysis of trends in the MCM rates. RESULTS: Outcome data for 9247 pregnancies showed a stable percentage of monotherapy to polytherapy prescribing habits over time. After Bonferroni correction, statistically significant (p<0.003) changes were found in monotherapy prescribing with increases in lamotrigine and levetiracetam and decreases in valproate and carbamazepine use. Between 1996 and 2016, the total MCM rate showed a 2.1% reduction per year (incidence risk ratio 0.979 (95% CIs 0.956 to 1.002) but Poisson regression analysis showed that this was not statistically significant p=0.08). CONCLUSION: Significant changes are seen in the prescribing habits in this cohort over 20 years, but a statistically significant change in the MCM rate was not detected. This work should be replicated on a larger scale to determine if significant changes are occurring in the MCM rate, which would allow a robust economic estimate of the benefits of improvements in prescribing practice and the personal effect of such changes.

An update on the recognition and treatment of non-convulsive status epilepticus in the intensive care unit.

INTRODUCTION: Non-convulsive status epilepticus (NCSE) is a complex and diverse condition which is often an under-recognised entity in the intensive care unit. When NCSE is identified the optimal treatment strategy is not always clear. Areas covered: This review is based on a literature review of the key literature in the field over the last 5-10 years. The articles were selected based on their importance to the field by the authors. Expert commentary: This review discusses the complex situations when a neurological consultation may occur in a critical care setting and provides an update on the latest evidence regarding the recognition of NCSE and the decision making around determining the aggressiveness of treatment. It also considers the ictal-interictal continuum of conditions which may be met with, particularly in the era of continuous EEG, and provides an approach for dealing with these. Suggestions for how the field will develop are discussed.

Plasma levels of intermedin (adrenomedullin-2) in healthy human volunteers and patients with heart failure.

Intermedin/adrenomedullin-2 (IMD) is a member of the adrenomedullin/CGRP peptide family. Less is known about the distribution of IMD than for other family members within the mammalian cardiovascular system, particularly in humans. The aim was to evaluate plasma IMD levels in healthy subjects and patients with chronic heart failure. IMD and its precursor fragments, preproIMD(25-56) and preproIMD(57-92), were measured by radioimmunoassay in 75 healthy subjects and levels of IMD were also compared to those of adrenomedullin (AM) and mid-region proadrenomedullin(45-92) (MRproAM(45-92)) in 19 patients with systolic heart failure (LVEF<45%). In healthy subjects, plasma levels (mean+SE) of IMD (6.3+0.6 pg ml(-1)) were lower than, but correlated with those of AM (25.8+1.8 pg ml(-1); r=0.49, p<0.001). Plasma preproIMD(25-56) (39.6+3.1 pg ml(-1)), preproIMD(57-92) (25.9+3.8 pg ml(-1)) and MRproAM(45-92) (200.2+6.7 pg ml(-1)) were greater than their respective bioactive peptides. IMD levels correlated positively with BMI but not age, and were elevated in heart failure (9.8+1.3 pg ml(-1), p<0.05), similarly to MRproAM(45-92) (329.5+41.9 pg ml(-1), p<0.001) and AM (56.8+10.9 pg ml(-1), p<0.01). IMD levels were greater in heart failure patients with concomitant renal impairment (11.3+1.8 pg ml(-1)) than those without (6.5+1.0 pg ml(-1); p<0.05). IMD and AM were greater in patients receiving submaximal compared with maximal heart failure drug therapy and were decreased after 6 months of cardiac resynchronization therapy. In conclusion, IMD is present in the plasma of healthy subjects less abundantly than AM, but is similarly correlated weakly with BMI. IMD levels are elevated in heart failure, especially with concomitant renal impairment, and tend to be reduced by high intensity drug or pacing therapy.