Hyperacute Detection of Neurofilament Heavy Chain in Serum Following Stroke: A Transient Sign

Serological biomarkers which enable quick and reliable diagnosis or measurement of the extent of irreversible brain injury early in the course of stroke are eagerly awaited. Neurofilaments (Nf) are a group of proteins integrated into the scaffolding of the neuronal and axonal cytoskeleton and an established biomarker of neuro-axonal damage. The Nf heavy chain (NfH(SMI35)) was assessed together with brain-specific astroglial proteins GFAP and S100B in hyperacute stroke (6 and 24 h from symptom onset) and daily for up to 6 days. Twenty-two patients with suspected stroke (median NIHSS 8) were recruited in a prospective observational study. Evidence for an ischaemic or haemorrhagic lesion on neuroimaging was found in 18 (ischaemia n = 16, intracerebral haemorrhage n = 2). Serum NfH(SMI35) levels became detectable within 24 h post-stroke (P < 0.0001) and elevated levels persisted over the study course. While GFAP was not detectable during the entire course, S100B levels peaked at the end of the observation period. The data indicate that significant in vivo information on the pathophysiology of stroke may be obtained by the determination of NfH(SMI35). Further studies are required to evaluate whether NfH(SMI35) in hyperacute stroke reflects the extent of focal ischaemic injury seen on neuroimaging or is a consequence of more diffuse neuro-axonal damage

eLearning resources to supplement postgraduate neurosurgery training.

BACKGROUND: In an increasingly complex and competitive professional environment, improving methods to educate neurosurgical residents is key to ensure high-quality patient care. Electronic (e)Learning resources promise interactive knowledge acquisition. We set out to give a comprehensive overview on available eLearning resources that aim to improve postgraduate neurosurgical training and review the available literature. MATERIAL AND METHODS: A MEDLINE query was performed, using the search term "electronic AND learning AND neurosurgery". Only peer-reviewed English-language articles on the use of any means of eLearning to improve theoretical knowledge in postgraduate neurosurgical training were included. Reference lists were crosschecked for further relevant articles. Captured parameters were the year, country of origin, method of eLearning reported, and type of article, as well as its conclusion. eLearning resources were additionally searched for using Google. RESULTS: Of n = 301 identified articles by the MEDLINE search, n = 43 articles were analysed in detail. Applying defined criteria, n = 28 articles were excluded and n = 15 included. Most articles were generated within this decade, with groups from the USA, the UK and India having a leadership role. The majority of articles reviewed existing eLearning resources, others reported on the concept, development and use of generated eLearning resources. There was no article that scientifically assessed the effectiveness of eLearning resources (against traditional learning methods) in terms of efficacy or costs. Only one article reported on satisfaction rates with an eLearning tool. All authors of articles dealing with eLearning and the use of new media in neurosurgery uniformly agreed on its great potential and increasing future use, but most also highlighted some weaknesses and possible dangers. CONCLUSION: This review found only a few articles dealing with the modern aspects of eLearning as an adjunct to postgraduate neurosurgery training. Comprehensive eLearning platforms offering didactic modules with clear learning objectives are rare. Two decades after the rise of eLearning in neurosurgery, some promising solutions are readily available, but the potential of eLearning has not yet been sufficiently exploited

UK consensus on pregnancy in multiple sclerosis: ‘Association of British Neurologists’ guidelines

Multiple sclerosis (MS) is more common in women than men and is most commonly diagnosed in early adulthood; thus, many patients will not have completed their families at the time of diagnosis. There is increasing awareness of the importance of early treatment in preventing long-term disability in MS. Delaying treatment until women with MS have completed their families can lead to the development of irreversible disability in at least some cases. It is therefore important to discuss family planning and pregnancy proactively. However, to date there is limited evidence to inform such discussions. We set out to develop consensus guidelines for the treatment of MS in pregnancy to encourage and facilitate discussions in this important area. The guidelines draw on available evidence from drug-specific pregnancy registers and published literature and have been scored by a panel of experts from a variety of disciplines using modified Delphi criteria. They cover prepregnancy counselling, management during pregnancy, delivery and anaesthetic options, postpartum advice and specific advice regarding currently licensed disease-modifying drugs. As the complexity and range of available disease-modifying drugs increase, further data gathering via a UK-wide MS pregnancy register is recommendedMS Trus

Brain-derived neurotrophic factor modulates nociceptive sensory inputs and NMDA-evoked responses in the rat spinal cord.

Central sensitization, the hyperexcitability of spinal processing that often accompanies peripheral injury, is a major component of many persistent pain states. Here we report that the neurotrophin, brain-derived neurotrophic factor (BDNF), is a modulator of excitability within the spinal cord and contributes to the mechanism of central sensitization. BDNF, localized in primary sensory neuron cell bodies and central terminals, potentiates nociceptive spinal reflex responses in an in vitro spinal cord preparation and induces c-fos expression in dorsal horn neurons. NMDA receptor-mediated responses, known as a major contributor to central sensitization, were significantly enhanced by exogenous BDNF. Systemic NGF treatment, a procedure that mimics peripheral inflammatory states, raises BDNF levels in sensory neurons and increases nociceptive spinal reflex excitability. This increased central excitability is reduced by trkB-IgG, a BDNF "antagonist." We also show directly that inflammatory pain-related behavior depends on BDNF release in vivo. Thus behavioral nociceptive responses induced by intraplantar formalin and by intraplantar carageenan are significantly attenuated by trkB-IgG. Hence BDNF is appropriately localized and regulated in inflammatory states and is sufficient and necessary for the expression of central sensitization in the spinal cord. We propose that BDNF may function as a modulator of central sensitization in pathological states, and our results suggest that pharmacological antagonism of BDNF may prove an effective and novel analgesic strategy for the treatment of persistent inflammatory pain states

Estrogen metabolizing enzymes in endometrium and endometriosis

BACKGROUND: Estradiol (E(2)) is an important promoter of the growth of both eutopic and ectopic endometrium. The findings with regard to the expression and activity of steroidogenic enzymes in endometrium of controls, in endometrium of endometriosis patients and in endometriotic lesions are not consistent. METHODS: In this study, we have looked at the mRNA expression and protein levels of a range of steroidogenic enzymes [aromatase, 17beta-hydroxysteroid dehydrogenases (17beta-HSD) type 1, 2 and 4, estrogen sulfotransferase (EST) and steroid sulfatase (STS)] in eutopic and ectopic endometrium of patients (n = 14) with deep-infiltrative endometriosis as well as in disease-free endometrium (n = 48) using real-time PCR and immunocytochemistry. In addition, we evaluated their menstrual cycle-related expression patterns, and investigated their steroid responsiveness in explant cultures. RESULTS: Aromatase and 17beta-HSD type 1 mRNA levels were extremely low in normal human endometrium, while mRNAs for types 2 and 4 17beta-HSD, EST and STS were readily detectable. Only 17beta-HSD type 2 and EST genes showed sensitivity to progesterone in normal endometrium. Types 1 and 2 17beta-HSD and STS protein was detected in normal endometrium using new polyclonal antibodies. CONCLUSIONS: In endometriosis lesions, the balance is tilted in favor of enzymes producing E(2). This is due to a suppression of types 2 and 4 17beta-HSD, and an increased expression of aromatase and type 1 17beta-HSD in ectopic endometrium

Blood biomarkers for the diagnosis of acute cerebrovascular diseases: a prospective cohort study

&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; The diagnosis of stroke or TIA in the emergency department is difficult, though important for early treatment. Circulating biomarkers might improve upon clinical assessment at admission.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Methods:&lt;/b&gt; We recruited symptomatic patients with suspected stroke or TIA and drew blood soon after admission. Each patient was assessed with the Face Arm Speech Test (FAST). We measured a panel of 15 circulating inflammatory, thrombotic, cardiac, and cerebral tissue damage biomarkers. Improvement in diagnostic performance was assessed by adding biomarkers to the FAST in logistic regression models to predict a final diagnosis of stroke or TIA (verified by expert review and imaging).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; 405 patients had suspected stroke: 285 with TIA or stroke (230 definite or probable ischemic stroke, 40 TIA, 15 hemorrhagic stroke) and 120 with other diagnoses. Only the markers t-PA and NT-proBNP were associated positively and significantly (p &#60; 0.01) with a diagnosis of TIA or stroke. The FAST had a sensitivity of 82% (95% CI 78-87) and specificity of 38% (95% CI 29-46) for the diagnosis of TIA or stroke. No biomarker individually improved the sensitivity or specificity of the FAST. A model containing the FAST, age, systolic blood pressure, NT-proBNP and t-PA had a better sensitivity (88%, p &#60; 0.006) and a better specificity (48%, p = 0.04) than the FAST test alone.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; No single blood marker improved the diagnostic performance of a validated clinical stroke scale. Panels of biomarkers may marginally improve diagnosis, but their practicability is uncertain, and requires further study.&lt;/p&gt