The influence of status epilepticus on adeno-pituitary hormone secretion in man : with special reference to prolactin

Epileptic seizures as well as antiepileptic drugs (AED) may interfere with the hypothalamicpituitary axis (HPA) and have neuroendocrine effects. A transient increase of prolactin (PRL) and cortisol in serum after generalised tonic-clonic or complex partial seizures has been one of the most consistent findings, although absences and myoclonic seizures, as well as seizures of very short duration, do not seem to affect PRL levels. The observation of a PRL increase in connection with epileptic seizures has been used as an aid in differentiating epileptic seizures from psychogenic attacks mimicking epileptic symptoms. In our first study we hypothesised that PRL measurement could also be used to help classify different forms of status epilepticus (SE). However, we found no PRL increase during SE in 15 patients, irrespective of SE type and AED treatment. This finding was confirmed in an extended series of 32 patients with 34 episodes of SE, also as compared with control levels of PRL on a seizure-free day in 16 of the patients Cellular depletion of PRL due to long-standing epileptic activity was discussed as a possible mechanism behind the normal PRL levels in SE. We investigated PRL secretion in patients with SE in two studies by interfering with two different aspects of the PRL regulatory system. In the first, we administered metoclopramide, a dopamine receptor blocker, i.v. in connection with nine cases of SE, and in the second, thyrotropin-releasing hormone (TRH) i.v. in seven cases of SE. PRL levels increased in response to the injections in all cases. Thus we found no evidence for cellular depletion. Since growth hormone (GH) and PRL partly share regulating substances, we decided also to study GH serum concentrations in connection with SE. GH levels were normal in 15 cases of SE, irrespective of type of SE and AED treatment. To broaden our understanding of how epilepsy may affect the HPA, we studied patients with epilepsy under three different conditions: interictally during seizure-free periods (n=6), postictally immediately after a single seizure (n=6), and during SE (n=7). The responses of PRL, GH, cortisol, and TSH to TRH were investigated. PRL was elevated in the postictal group, with a further distinct increase after TRH administration. GH levels were normal in relation to seizure activity irrespective of seizure duration, whereas paradoxical GH responses to TRH were seen after both single seizures and SE. Cortisol levels were elevated after epileptic seizures, and this increase was maintained during SE. TSH reactivity to TRH seemed less pronounced in the SE group than in the postictal. Results in the interictal group were similar to those observed in healthy control subjects. Our results demonstrate that both short- and long-standing epileptic seizure activity can alter pituitary hormone concentrations in serum, probably through influences on the regulation of the HPA. The hormonal changes seem related to the actual seizure activity, and not to the epilepsy disorder, nor to the metabolic condition of the patient or the AED treatment

M Protein, a Classical Bacterial Virulence Determinant, Forms Complexes with Fibrinogen that Induce Vascular Leakage

AbstractIncreased vascular permeability is a key feature of inflammatory conditions. In severe infections, leakage of plasma from the vasculature induces a life-threatening hypotension. Streptococcus pyogenes, a major human bacterial pathogen, causes a toxic shock syndrome (STSS) characterized by excessive plasma leakage and multi-organ failure. Here we find that M protein, released from the streptococcal surface, forms complexes with fibrinogen, which by binding to β2 integrins of neutrophils, activate these cells. As a result, neutrophils release heparin binding protein, an inflammatory mediator inducing vascular leakage. In mice, injection of M protein or subcutaneous infection with S. pyogenes causes severe pulmonary damage characterized by leakage of plasma and blood cells. These lesions were prevented by treatment with a β2 integrin antagonist. In addition, M protein/fibrinogen complexes were identified in tissue biopsies from a patient with necrotizing fasciitis and STSS, further underlining the pathogenic significance of such complexes in severe streptococcal infections

The provision of epilepsy care across Europe 2017:a 17-year follow-up survey

\u3cp\u3eObjective: To assess the resources available in the provision of epilepsy care across Europe and the developments since the International League Against Epilepsy (ILAE) survey published in 2003 (data collected in 2000). Methods: An updated online version of the European Epilepsy Services Inventory was distributed to all European chapters of the ILAE (N = 47) and responses were obtained from 33 chapters (response rate 70%). To assess trends and allow comparisons with the survey published in 2003, the responding countries were divided into 4 groups (Western, Central, Southern, and Eastern). Responses from European Union (EU) member states are reported as a subgroup (N = 23), since the current survey is a part of the EU-funded European Study on the Burden and Care of Epilepsy (ESBACE, www.esbace.eu). Results: The total number of physicians involved in epilepsy care had increased since 2000, with the largest increase seen for neurologists. The gap between the best- and the least-provided areas with regard to the competence of the providers had diminished. However, the density of comprehensive multidisciplinary epilepsy teams had not changed to any greater degree. The main problems reported by the chapters were to a large extent the same as in 2000 and included lack of specialists and specialist care, lack or underuse of epilepsy surgery, and problems regarding financing and resource allocation. Several chapters also highlighted problems with healthcare structure and organization. Significance: Although there have been some improvements concerning the availability of care for people with epilepsy in Europe over the last 17 years, there are still a number of problem areas with little improvement or where there are important regional differences.\u3c/p\u3