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    Cranial autonomic ganglia in headache disorders

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    Headache disorders are amongst the most prevalent causes of disability worldwide. Most of the effort to develop new therapeutics has focused on migraine. Patients suffering from less common headache disorders such as trigeminal neuralgia (TN) or cluster headache (CH) are also in need of new and better treatments. Our group has developed a new navigation based surgical tool that allows accurate targeting of small anatomical structures that might be involved in cranial and facial pain. Two previous pilot trials have used this technique to inject botulinum toxin type A (BTA) towards the sphenopalatine ganglion (SPG) in 10 patients with intractable chronic CH (1) and in 10 patients with intractable chronic migraine (2). In this Thesis, we further explore the possibilities of this new device. Most of the studies targeting the SPG do not localize the ganglion directly and use anatomical landmarks which have not been validated (3). Our group has depicted the SPG in living humans using MRI for the first time (4). Nonetheless, MRI might not always be available or some patients might have medical contraindications to undergo this examination. For this reason, we developed an algorithm to predict the location of the SPG using bony landmarks identified in CT-scans (paper 1). Classical TN is not classified under trigeminal autonomic cephalalgias but recent studies have shown that one third of the patients might present autonomic symptoms and the SPG has been involved in its pathophysiology. In paper 2, we conducted a pilot study with 10 patients with classical TN (ICHD-3 beta criteria). Patients were injected with 25 units (U) BTA towards the ipsilateral SPG. The primary outcome was the occurrence of adverse events (AEs). The main efficacy outcome was the number of TN attacks at weeks 5-8 after injection compared to baseline. CH is the most common trigeminal autonomic cephalalgia and it inflicts great suffering among patients. The SPG has been involved in its pathophysiology but no other cranial autonomic ganglia have been targeted in this condition. In paper 3 we describe the rational for the role of the otic ganglion (OG) in autonomic cephalalgias. The OG is a smaller and less studied cranial autonomic ganglion. It cannot be seen in CT-scans or in conventional MR imaging. Its relation to the mandibular nerve has been described to be constant in the literature, with the OG being in direct contact to the medial surface of the third division of the trigeminal nerve (5). The mandibular nerve can be easily localized in MRI. In order to target one structure, which cannot be directly depicted, at least one other anatomical landmark is necessary in addition to the mandibular nerve. The foramen ovale (FO) can be seen clearly in CT-images. One anatomicalcadaveric study describes that the OG “lies immediately below the FO”, however the distance between the FO and the OG was not reported in this study (5). In order to target the OG we measured the average distance between the FO and the OG in 21 high definition photographs of 21 infratemporal fossae from 18 cadavers (paper 3). In a pilot study with 10 patients with intractable chronic CH (paper 4), 5 patients were injected with 12.5 U of BTA and 5 patients with 25 U of BTA towards the ipsilateral OG. The primary endpoint was the occurrence of AEs. The main efficacy outcome was the number of attacks in month 2 after injection compared to baseline. Main findings of this Thesis: • The SPG localization can be predicted on CT-images using 2 bony landmarks. Localizing the SPG on CT-images will be important for patients with contraindications to undergo an MRI (e.g. claustrophobia, MR-incompatible metallic foreign bodies or stimulators, etc.), when access to MRI is limited, and in those patients where repeated injections are needed. • Injection of BTA towards the SPG in classical TN (ICHD-3 beta) appears to be safe. We did not find any indication for effect in reducing the number of TN attacks after injection of 25 U of BTA towards the SPG. A better understanding of the role of the SPG in TN is necessary. • The OG appears to have a constant location, being situated 4.5 mm inferior of the FO and medial to the mandibular nerve. The FO is easily localized on CT-scans and may be an interesting anatomical landmark when trying to develop navigation-based therapies towards the OG • Injection of BTA towards the OG in CH appears to be feasible and safe. We did not find a clear indication for effect in reducing the number of CH attacks after injection of 25 U of BTA towards the OG. A better description of the topography of the OG in living humans should precede further clinical studies targeting this structure

    Cranial autonomic ganglia in headache disorders

    No full text
    Headache disorders are amongst the most prevalent causes of disability worldwide. Most of the effort to develop new therapeutics has focused on migraine. Patients suffering from less common headache disorders such as trigeminal neuralgia (TN) or cluster headache (CH) are also in need of new and better treatments. Our group has developed a new navigation based surgical tool that allows accurate targeting of small anatomical structures that might be involved in cranial and facial pain. Two previous pilot trials have used this technique to inject botulinum toxin type A (BTA) towards the sphenopalatine ganglion (SPG) in 10 patients with intractable chronic CH (1) and in 10 patients with intractable chronic migraine (2). In this Thesis, we further explore the possibilities of this new device. Most of the studies targeting the SPG do not localize the ganglion directly and use anatomical landmarks which have not been validated (3). Our group has depicted the SPG in living humans using MRI for the first time (4). Nonetheless, MRI might not always be available or some patients might have medical contraindications to undergo this examination. For this reason, we developed an algorithm to predict the location of the SPG using bony landmarks identified in CT-scans (paper 1). Classical TN is not classified under trigeminal autonomic cephalalgias but recent studies have shown that one third of the patients might present autonomic symptoms and the SPG has been involved in its pathophysiology. In paper 2, we conducted a pilot study with 10 patients with classical TN (ICHD-3 beta criteria). Patients were injected with 25 units (U) BTA towards the ipsilateral SPG. The primary outcome was the occurrence of adverse events (AEs). The main efficacy outcome was the number of TN attacks at weeks 5-8 after injection compared to baseline. CH is the most common trigeminal autonomic cephalalgia and it inflicts great suffering among patients. The SPG has been involved in its pathophysiology but no other cranial autonomic ganglia have been targeted in this condition. In paper 3 we describe the rational for the role of the otic ganglion (OG) in autonomic cephalalgias. The OG is a smaller and less studied cranial autonomic ganglion. It cannot be seen in CT-scans or in conventional MR imaging. Its relation to the mandibular nerve has been described to be constant in the literature, with the OG being in direct contact to the medial surface of the third division of the trigeminal nerve (5). The mandibular nerve can be easily localized in MRI. In order to target one structure, which cannot be directly depicted, at least one other anatomical landmark is necessary in addition to the mandibular nerve. The foramen ovale (FO) can be seen clearly in CT-images. One anatomicalcadaveric study describes that the OG “lies immediately below the FO”, however the distance between the FO and the OG was not reported in this study (5). In order to target the OG we measured the average distance between the FO and the OG in 21 high definition photographs of 21 infratemporal fossae from 18 cadavers (paper 3). In a pilot study with 10 patients with intractable chronic CH (paper 4), 5 patients were injected with 12.5 U of BTA and 5 patients with 25 U of BTA towards the ipsilateral OG. The primary endpoint was the occurrence of AEs. The main efficacy outcome was the number of attacks in month 2 after injection compared to baseline. Main findings of this Thesis: • The SPG localization can be predicted on CT-images using 2 bony landmarks. Localizing the SPG on CT-images will be important for patients with contraindications to undergo an MRI (e.g. claustrophobia, MR-incompatible metallic foreign bodies or stimulators, etc.), when access to MRI is limited, and in those patients where repeated injections are needed. • Injection of BTA towards the SPG in classical TN (ICHD-3 beta) appears to be safe. We did not find any indication for effect in reducing the number of TN attacks after injection of 25 U of BTA towards the SPG. A better understanding of the role of the SPG in TN is necessary. • The OG appears to have a constant location, being situated 4.5 mm inferior of the FO and medial to the mandibular nerve. The FO is easily localized on CT-scans and may be an interesting anatomical landmark when trying to develop navigation-based therapies towards the OG • Injection of BTA towards the OG in CH appears to be feasible and safe. We did not find a clear indication for effect in reducing the number of CH attacks after injection of 25 U of BTA towards the OG. A better description of the topography of the OG in living humans should precede further clinical studies targeting this structure

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Multidisciplinary consensus guideline for the diagnosis and management of spontaneous intracranial hypotension

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    Background We aimed to create a multidisciplinary consensus clinical guideline for best practice in the diagnosis, investigation and management of spontaneous intracranial hypotension (SIH) due to cerebrospinal fluid leak based on current evidence and consensus from a multidisciplinary specialist interest group (SIG).Methods A 29-member SIG was established, with members from neurology, neuroradiology, anaesthetics, neurosurgery and patient representatives. The scope and purpose of the guideline were agreed by the SIG by consensus. The SIG then developed guideline statements for a series of question topics using a modified Delphi process. This process was supported by a systematic literature review, surveys of patients and healthcare professionals and review by several international experts on SIH.Results SIH and its differential diagnoses should be considered in any patient presenting with orthostatic headache. First-line imaging should be MRI of the brain with contrast and the whole spine. First-line treatment is non-targeted epidural blood patch (EBP), which should be performed as early as possible. We provide criteria for performing myelography depending on the spine MRI result and response to EBP, and we outline principles of treatments. Recommendations for conservative management, symptomatic treatment of headache and management of complications of SIH are also provided.Conclusions This multidisciplinary consensus clinical guideline has the potential to increase awareness of SIH among healthcare professionals, produce greater consistency in care, improve diagnostic accuracy, promote effective investigations and treatments and reduce disability attributable to SIH

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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