VACCINATION AGAINST SWINE FLU CAUSED NARCOLEPSY IN SEVERAL EUROPEAN COUNTRIES

Publisher Copyright: © 2020 Boström I., Lindberger O., Partinen M., Landtblom A.M. All Rights Reserved.Narcolepsy is a rare sleeping disorder that gives sleep onset rapid eye movement periods and excessive daytime sleepiness. It is divided into two subgroups, narcolepsy type 1 where there also is orexin deficiency and cataplexy and narcolepsy type 2 that lack these features. Narcolepsy type 1 is assumed to be an autoimmune disease with destruction of orexin-producing cells. The pathology behind is unclear. There is a strong association to a class II HLA allele, HLADQB1*06:02 and the H1N1-virus and streptococcal infections has also been associated with narcolepsy. The severity of narcolepsy differs between patients from those who can manage their disease without medication to those who has a severe impact on their everyday life. There is a diagnostic delay between the onset of symptoms and time for diagnosis that in some cases can be more than a decade. The global mean prevalence is 30 per 100 000 inhabitants. The incidence in children in northern Europe has risen since 2010. An early study of the 2009 H1N1 influenza A pandemic indicated a high mortality and prompted efforts to rapidly come up with a vaccine. One of these was Pandemrix that was the most widely used in Europe and 61 % of the inhabitants in Sweden was vaccinated. Studies have shown an increased incidence of narcolepsy type 1 in European countries that had used Pandemrix, but no increased risk was seen in countries that had used other vaccines than Pandemrix.Peer reviewe

Cerebral microdialysis in clinical studies of drugs: pharmacokinetic applications

The ability to deliver drug molecules effectively across the blood–brain barrier into the brain is important in the development of central nervous system (CNS) therapies. Cerebral microdialysis is the only existing technique for sampling molecules from the brain extracellular fluid (ECF; also termed interstitial fluid), the compartment to which the astrocytes and neurones are directly exposed. Plasma levels of drugs are often poor predictors of CNS activity. While cerebrospinal fluid (CSF) levels of drugs are often used as evidence of delivery of drug to brain, the CSF is a different compartment to the ECF. The continuous nature of microdialysis sampling of the ECF is ideal for pharmacokinetic (PK) studies, and can give valuable PK information of variations with time in drug concentrations of brain ECF versus plasma. The microdialysis technique needs careful calibration for relative recovery (extraction efficiency) of the drug if absolute quantification is required. Besides the drug, other molecules can be analysed in the microdialysates for information on downstream targets and/or energy metabolism in the brain. Cerebral microdialysis is an invasive technique, so is only useable in patients requiring neurocritical care, neurosurgery or brain biopsy. Application of results to wider patient populations, and to those with different pathologies or degrees of pathology, obviously demands caution. Nevertheless, microdialysis data can provide valuable guidelines for designing CNS therapies, and play an important role in small phase II clinical trials. In this review, we focus on the role of cerebral microdialysis in recent clinical studies of antimicrobial agents, drugs for tumour therapy, neuroprotective agents and anticonvulsants