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Objective To identify grey matter alterations in patients suffering new daily persistent headache to enrich the pathophysiological concept of this rare headache disorder characterised by a distinct, clearly remembered onset and its instant chronification. Method Magnetic resonance-based voxel-based and surface-based morphometry was used to investigate 23 patients suffering from new daily persistent headache and 23 age- and gender-matched healthy controls with 1.5 Tesla MRI. Independent statistical analysis was performed at three sites using statistical parametric mapping, as well as FSL(FMRIB Software Library)-based approaches. Results No grey matter changes were detected using this sophisticated and cross-checked method. Conclusion The absence of structural brain changes in patients with new daily persistent headache contribute to the recent discussion regarding structural alterations in primary headache disorders in general and does not provide evidence for grey matter changes being associated with the pathophysiology of new daily persistent headache. Future research will have to determine the underlying pathophysiological mechanisms of this disorder.

Erenumab is a monoclonal antibody, targeted against the calcitonin gene-related peptide (CGRP) receptor. Clinical studies have demonstrated prophylactic efficacy in both episodic (EM) and chronic migraine (CM). The aim of the present study is to evaluate the efficacy of treatment in tertiary headache centers under real-life conditions. In a retrospective analysis, the period of 3 months before and after initiation of erenumab therapy was compared. Relevant parameters (headache days, headache intensity, headache duration, acute medication, previous prophylaxis treatments) were collected from medical charts of all migraine patients (N = 82) who started treatment with erenumab between November 1st 2018 and May 1st 2019 at two tertiary headache centers in Germany. The sample included 68 female (82.9%) and 14 male patients aged between 22 and 78 years (mean 51.1 years, SD 10.5 years). Of these patients, 57.3% met the criteria for CM and 56.9% overused acute medication. Under therapy with erenumab, a significant reduction of headache days was observed from the first month on. The effect was most pronounced in the third month with a decrease in monthly headache days from 16.6 to 11.6 days (p p = 0.004) and average duration of headache attacks (p = 0.016). The 50% responder rate in patients with CM was lower in the first month compared to EM but then increased similarly to EM. Patients with medication overuse (MO) also responded to the therapy. There was a reduction in medication overuse from 57% at baseline to 29% after therapy (p = 0.011). Overall, a positive result of treatment with erenumab can be shown in a highly selected sample with severely affected migraine patients and a refractory course prior to treatment. This re-confirms the clinical trial data also for this highly selected group.

Headache is frequent in patients with mitochondrial disorders. Previous studies point to a higher prevalence of headache in these patients than in the general population. As mitochondrial disorders often present a variety of other symptoms, the question arises how much the presence of headache really influences daily life. We performed a cross-sectional, questionnaire-based study investigation with 61 patients with a genetically proved mitochondrial disease mainly composed of CPEO phenotype. Headache was examined using a standardized questionnaire, and classified according to ICHD-2. Headache-related disability was evaluated by the Headache-Impact-Test-6 (HIT-6). Additionally, depression and anxiety were examined using the Hospital Anxiety and Depression Scale (HADS) and Short-Form-Health Survey (SF-12) was used to investigate the health-related quality of life. Headache was reported by 43/61 (70.5%) of the patients. 35/61 patients (57.4%) described a Tension-type headache (TTH) and 26 patients (42.6%) a migraine. Patients reporting headache had a significantly higher HIT-6 score than those without (mean: 54.47 vs. 38.47, p p

BACKGROUND Even using predictive formulas based on anthropometrics in about 30% of subjects, liver weight (LW) cannot be predicted with a ≤20% margin of error. We aimed to identify factors associated with discrepancies between predicted and observed LW. METHODS In 500 consecutive liver grafts, we tested LW predictive performance using 17 formulas based on anthropometric characteristics. Hashimoto's formula (961.3 × BSA_D-404.8) was associated with the lowest mean absolute error and used to predict LW for the entire cohort. Clinical factors associated with a ≥20% margin of error were identified in a multivariable analysis after propensity score matching (PSM) of donors with similar anthropometric characteristics. RESULTS The total LW was underestimated with a ≥20% margin of error in 53/500 (10.6%) donors and overestimated in 62/500 (12%) donors. After PSM analysis, ages ≥ 65, (OR = 3.21; CI95% = 1.63-6.31; P = .0007), age ≤ 30 years, (OR = 2.92; CI95% = 1.15-7.40; P = .02), and elevated gamma-glutamyltransferase (GGT) levels (OR = 0.98; CI95% = 0.97-0.99; P = .006), influenced the risk of LW overestimation. Age ≥ 65 years, (OR = 5.98; CI95% = 2.28-15.6; P = .0002), intensive care unit (ICU) stay with ventilation > 7 days, (OR = 0.32; CI95% = 0.12-0.85; P = .02) and waist circumference increase (OR = 1.02; CI95% = 1.00-1.04; P = .04) were factors associated with LW underestimation. CONCLUSIONS Increased waist circumference, age, prolonged ICU stay with ventilation, elevated GGT were associated with an increase in the margin of error in LW prediction. These factors and anthropometric characteristics could help transplant surgeons during the donor-recipient matching process.

Background Although migraine is less common in older people, preventive treatment of migraine in these individuals may be more challenging due to the presence of multiple comorbidities and polypharmacy. Additionally, evidence for migraine treatment efficacy, safety, and tolerability is limited in this population. We evaluated efficacy, safety, and tolerability of fremanezumab, a fully humanized monoclonal antibody (IgG2Δa) that selectively targets calcitonin gene–related peptide (CGRP), in clinical trial participants aged ≥60 years with episodic migraine (EM) or chronic migraine (CM). Methods This analysis included data from 3 randomized, double-blind, placebo-controlled phase 3 studies: the HALO EM study, HALO CM study, and FOCUS study in participants with EM or CM and prior inadequate response to 2–4 migraine preventive medication classes. Participants in all studies were randomized 1:1:1 to receive 12 weeks of subcutaneous treatment with quarterly fremanezumab (Months 1/2/3: EM/CM, 675 mg/placebo/placebo), monthly fremanezumab (Months 1/2/3: EM, 225 mg/225 mg/225 mg; CM, 675 mg/225 mg/225 mg), or matched monthly placebo. Results These pooled analyses included 246 participants aged ≥60 years. Reductions in monthly migraine days from baseline over 12 weeks were significantly greater with fremanezumab (least-squares mean change from baseline [standard error]: quarterly fremanezumab, − 4.3 [0.59]; monthly fremanezumab, − 4.6 [0.54]) versus placebo (placebo, − 2.3 [0.57]; both P P P N = 2843). Conclusions This pooled subgroup analysis demonstrates that fremanezumab treatment is efficacious and well-tolerated over 12 weeks in participants aged ≥60 years with EM or CM. These data may help healthcare providers with clinical decision making and preventive treatment selection for older patients with migraine. Trial registration ClinicalTrials.gov identifiers: HALO CM: NCT02621931; HALO EM: NCT02629861; FOCUS: NCT03308968.

Background Gastrointestinal (GI) bleeding is a common indication for endoscopy. For refractory cases, hemostatic powders (HP) represent "touch-free" agents. Aim To analyze short term (ST-within 72 h-) and long-term (LT-within 30 d-) success for achieving hemostasis with HP and to directly compare the two agents Hemospray (HS) and Endoclot (EC). Methods HP was applied in 154 consecutive patients (mean age 67 years) with GI bleeding. Patients were followed up for 1 mo (mean follow-up: 3.2 mo). Results Majority of applications were in upper GI tract (89%) with following bleeding sources: peptic ulcer disease (35%), esophageal varices (7%), tumor bleeding (11.7%), reflux esophagitis (8.7%), diffuse bleeding and erosions (15.3%). Overall ST success was achieved in 125 patients (81%) and LT success in 81 patients (67%). Re-bleeding occurred in 27% of all patients. In 72 patients (47%), HP was applied as a salvage hemostatic therapy, here ST and LT success were 81% and 64%, with re-bleeding in 32%. As a primary hemostatic therapy, ST and LT success were 82% and 69%, with re-bleeding occurring in 22%. HS was more frequently applied for upper GI bleeding (P = 0.04). Conclusion Both HP allow for effective hemostasis with no differences in ST, LT success and re-bleeding.

Mitochondrial processes may play a role in the pathophysiology of migraine. Serum levels of two biomarkers, Fibroblast-growth-factor 21 (FGF-21) and Growth-differentiation-factor 15 (GDF-15), are typically elevated in patients with mitochondrial disorders. The study investigated whether the presence of migraine may influence FGF-21 and GDF-15 serum levels considering vascular and metabolic disorders as possible confounders. A cross-sectional study in two headache centers was conducted analyzing GDF-15 and FGF-21 serum concentration in 230 patients with episodic and chronic migraine compared to a control group. Key clinical features of headache were evaluated, as well as health-related life quality, anxiety and depression using SF-12 and HADS-questionnaires. Elevated GDF-15 values were detected in the migraine group compared to the control group (506.65 ± 275.87 pg/mL vs. 403.34 ± 173.29 pg/mL, p &lt, 0.001, Mann–Whitney U test). A strong correlation between increasing age and higher GDF-15 levels was identified (p &lt, 0.001, 95%-CI elevation of GDF-15 per year 5.246–10.850 pg/mL, multiple linear regression). Mean age was different between the groups, and this represents a confounding factor of the measurements. FGF-21 levels did not differ between migraine patients and controls (p = 0.635, Mann–Whitney U test) but were significantly influenced by increasing BMI (p = 0.030, multiple linear regression). Neither biomarker showed correlation with headache frequency. Higher FGF-21 levels were associated with a higher mean intensity of headache attacks, reduced health-related life quality and anxiety. When confounding factors were considered, increased serum levels of FGF-21 and GDF-15 were not detected in migraine patients. However, the results show an age-dependence of GDF-15 in migraine patients, and this should be considered in future studies. Similar findings apply to the relationship between FGF-21 and BMI. Previous studies that did not adjust for these factors should be interpreted with caution.

Background Persistent postural-perceptual dizziness (PPPD) is the most common functional vestibular disorder. A multisensory mismatch altered by psychological influences is considered to be an important pathophysiological mechanism. Increased cortical and subcortical excitability may play a role in the pathophysiology of PPPD. We hypothesized that decreased motion perception thresholds reflect one mechanism of the abnormal vestibular responsiveness in this disorder. We investigated the vestibular perception thresholds and the vestibular ocular reflex with a rotatory chair experiment to gain insights in the processing and adaption to vestibular provocation. Methods In this cross-sectional study 26 female PPPD patients and 33 healthy female age matched controls (HC) were investigated sitting in a motorized rotary chair shielded regarding visual and acoustic stimuli. The chair was rotated for 20 minutes with slowly increasing velocity to a maximum of 72°/s. We functionally tested motion perception thresholds and vegetative responses to rotation as well as vestibular-ocular reflex thresholds. We additionally investigated several psychological comorbidities (i.e. depression, anxiety, somatosensory amplification) using validated scores. Conventional dizziness scores were obtained to quantify the experienced dizziness and impact on daily life. Results PPPD patients showed a significant reduced vestibulo-perceptual threshold (PPPD: 10.9°/s vs. HC: 29.5°/s; pp=0.043). No significant difference was measured regarding nystagmus parameters between both groups. Conclusion PPPD patients showed increased vegetative response as well as decreased vestibulo-perceptual thresholds which are related to disease duration. This is of interest as PPPD might be sustained by increased vestibular excitability leading to motion intolerance and induction of dizziness when exposed to movement.

Background The prevalence of migraine and non-migraine headache declines with age. Methods Data from the third visit (2011–2015) of the population-based Heinz Nixdorf Recall study were analysed (n = 2038, 51% women, 65–86 years). Possible risk factors for headache activity (obesity, education, smoking, sports, alcohol, partnership status, living alone, having children, sleep quality, depression, hypertension, diabetes mellitus, stroke, coronary heart disease, medication), and headache symptoms were assessed. We estimated the lifetime prevalence and the prevalence of current active headache of migraine with and without aura, and non-migraine headache. The associations between possible risk factors and headache activity (active vs. inactive) were estimated by age and sex-adjusted odds ratios and 95% confidence intervals (OR [95% CI]) using multiple logistic regression. Results The lifetime prevalence of migraine was 28.6% (n = 584). One hundred and ninety-two (9.4%) had still-active migraine, 168 (3.5%) had migraine with aura, and 416 (5.9%) had migraine without aura. One hundred and sixty-eight (8.2%) had “episodic infrequent migraine, 0–8 headache days/month”, 10 (0.5%) had “episodic frequent migraine, 9–14 headache days/month”, and five (0.2%) had “chronic migraine, ≥15 headache days/month”. Overall, 10 (0.5%) had “chronic headache, any headache on ≥15 days/month”. Female gender and younger age were the most important associated migraine risk factors. Depression (1.62 [1.06; 2.47]) and poor sleep (1.06 [1.00; 1.12]) were associated with migraine and headache activity in general. Antihypertensives were associated with headache remission (0.80 [0.64; 1.00]). Additionally, undertaking less sports (0.72 [0.51; 1.03]) was associated with higher migraine activity. Conclusions Headaches and migraines are not rare in the older population. They are related to mood and sleep disturbance, and migraine even to less physical activity. Antihypertensives are related to headache remission.

Background and purpose Vestibular migraine (VM) patients are ictally and interictally hypersensitive for self-motion and visual perception. Increased cortical excitability of the vestibular system represented by lowered motion perception thresholds might play an important role in the pathophysiology of VM. We aimed to compare motion perception thresholds and the vegetative response to rotatory motion, as well as the vestibulo-ocular reflex (VOR) during rotation in VM patients compared to healthy controls (HC). Methods In this cross-sectional study, 28 female VM patients in the interictal state and 33 age- and gender-matched HC were investigated sitting in a motorized rotary chair shielded regarding visual and acoustic stimuli for 20 min with slowly increasing velocity (maximum = 72°/s). The motion perception threshold was indicated by the participants by pushing a button. During and after rotation, participants rated the presence and extent of motion sickness using a sickness rating scale. Results We detected lower motion perception thresholds (7.54°/s vs. 23.49°/s; p < 0.001) in VM patients compared to HC but no difference at the basic VOR thresholds. Furthermore, the patients showed enhanced susceptibility to motion sickness during and after the rotation. Conclusions We provide evidence for decreased motion perception thresholds and pronounced susceptibility to motion sickness in VM patients in the interictal state, which could indicate alterations in higher levels of vestibular processing. Future studies should determine whether this could be the pathophysiological hallmark of VM either as a unique disease entity or in differentiation from other forms of migraine.

Anthropometric parameters (weight, height) are usually used for quick matching between two individuals (donor and recipient) in liver transplantation (LT). This study aimed to evaluate clinical factors influencing the overall available space for implanting a liver graft in cirrhotic patients. In a cohort of 275 cirrhotic patients undergoing LT, we calculated the liver volume (LV), cavity volume (CV), which is considered the additional space between the liver and the right hypocondrium, and the overall volume (OV = LV + CV) using a computed tomography (CT)-based volumetric system. We then chose the formula based on anthropometric parameters that showed the best predictive value for LV. This formula was used to predict the OV in the same population. Factors influencing OV variations were identified by multivariable logistic analysis. The Hashimoto formula (961.3 × BSA_D-404.8) yielded the lowest median absolute percentage error (21.7%) in predicting the LV. The median LV was 1531 ml. One-hundred eighty-five patients (67.2%) had a median CV of 1156 ml (range: 70–7006), and the median OV was 2240 ml (range: 592–8537). Forty-nine patients (17%) had an OV lower than that predicted by the Hashimoto formula. Independent factors influencing the OV included the number of portosystemic shunts, right anteroposterior abdominal diameter, model for end-stage liver disease (MELD) score > 25, high albumin value, and BMI > 30. Additional anthropometric characteristics (right anteroposterior diameter, body mass index) clinical (number of portosystemic shunts), and biological (MELD, albumin) factors might influence the overall volume available for liver graft implantation. Knowledge of these factors might be helpful during the donor–recipient matching.

Background. In myotonic dystrophy, a significantly increased potassium release upon exercise was previously described. However, it remained unclear so far whether this is a specific feature of myotonic dystrophies or a consequence of distal muscular weakness in general. Methods. We performed non-ischemic forearm exercise test (NIFET) and measured venous K+ concentration at rest and at three different force levels (20–30%, 50–60%, 70–80%) related to maximal contraction force (MCF) in patients with different myopathies (n = 7), motor neuropathies (n = 8) with distal phenotype and healthy volunteers (n = 12). The specific K+ production was defined as venous K+ increase related to workload. Results. Maximal contraction force, workload and venous K+ increase were lower at all force levels in both myopathy and neuropathy groups compared to the control group. With increasing workload, the control group showed a quasi-linear increase in K+ release, resulting in a nearly constant specific K+ production within the three force levels (p = 0.752, Kruskal-Wallis-Test). In contrast, in myopathies a higher specific K+ production was measured at low force levels (20-30% MCF) in comparison to higher force levels (p = 0.015, Kruskal-Wallis test). In neuropathies, the lowest specific K+ production was obtained at 20–30% MCF. At this force level, the specific K+ production was significantly higher in myopathies compared to neuropathies (Fig. 1; p = 0.005, Mann-Whitney U Test). At 50–60% and 70–80% MCF, the specific K+ values increasingly converged and did not significantly differ between the three groups (Fig. 1; p = 0.09 and p = 0.37, Kruskal-Wallis test). Conclusion. In our study, increased K+ efflux related to workload occurred in patients with myogenic in comparison to neurogenic distal muscular weakness at low force levels. High specific K+ production does not seem to be an exclusive feature of myotonic dystrophies but of myogenic muscular weakness in general. Our results point to a different regulation of K+ balance in neurogenic and myogenic muscular weakness possibly due to a different recruitment behaviour of motor units and the action potential frequency of motor neurons in neurogenic and myogenic processes. Fig. 1.

We systematically reviewed the literature on definitions and outcomes of large-for-size (LFS) syndrome in orthotopic liver transplantation (LT). This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Cochrane Library, PubMed, and Embase were searched (January 1990–January 2019) for studies reporting LFS in LT. Primary outcomes were definitions and mortality of LFS LT. Eleven studies reporting patients with LFS LT were identified. Four different formulas (graft-to-recipient weight ratio (GRWR), body surface area index (BSAi), donor standardized total liver volume (sTLV)–to–recipient sTLV ratio, and graft weight/right anteroposterior distance (RAP) ratio) with their critical thresholds were found. There were 81 patients (54% women) with a median weight and height of 62.5 kg (range, 40–105 kg) and 165 cm (range, 145–180 cm). The median graft weight was 1772 g (range, 1290–2400 g), and the median GWRW was 2.77% (range, 2.1–4.00%). Graft venous outflow obstruction was described in seven patients (8.6%). At the time of LT, fascial closure was not achieved in 24 patients (29.6%) and the graft size was reduced by a liver resection in three patients (3.7%). Thirteen deaths (16%) were reported in the first 90 postoperative days with two patients undergoing re-transplant. LFS LT remains heterogeneously defined but characterized by high mortality rates despite the use of tailored surgical solutions (graft reduction and open abdomen). A composite definition is proposed in order to better describe LFS clinical syndrome.

Background: Calcitonin gene related peptide (CGRP) monoclonal antibodies (mAB) are the first specific migraine prophylactic medication. Erenumab is the only CGRP mAB targeting the CGRP receptor. Clinical data regarding efficacy and tolerability of erenumab in highly therapy-refractory patients are not available, yet, although many patients treated with CGRP mAB under real world conditions can be considered as highly therapy-refractory.Methods: Clinical routine data of highly therapy-refractory migraine patients treated with erenumab 70mg for three months between November 2018 and December 2019 in the West German Headache Center, University Hospital Essen, Germany, were analysed. Monthly migraine days (MMD), monthly headache days (MHD) and days of acute medication intake (AMD) were assessed. Statistical analysis was performed using the Wilcoxon test. Descriptive statistics were performed to evaluate changes of vegetative symptoms, acute medication response, side effects, as well as treatment satisfaction.Results: Complete clinical data were available for 26 episodic (EM) and 74 chronic (CM) migraineurs. Sixty-six % (n=49) of CM patients had an additional medication overuse headache (MOH). After three months 57.7 % of EM patients and 41.9 % of CM patients had a 50% or greater reduction of MMD. The mean number of MMD was reduced by 3.43 (SE 1.26) in EM, and by 4.72 (SE 0.87) in CM. Thirty-nine patients (52.7%) returned from chronic to episodic course of migraine. After three months, 23 patients (46.9%) were not suffering from a MOH anymore.Conclusions: Erenumab seems to be a promising therapeutic option in highly therapy-refractory migraine patients.Trial registration: Retrospective registered.

The presence of high endothelial venules (HEVs) in the tumor micro-environment is associated with favorable clinical out-come in breast cancer and other human solid tumors. HEVs can be highlighted in tissue samples by MECA-79 immunohistochemistry. HEVs are heterogeneously scattered in the tumor micro-environment, preferentially in areas infiltrated by lymphocytes, and their density must be assessed at high resolution on whole slide in the tumor area. We present a frame-work for HEV detection through classification of MECA-79 immunostaining in whole slide images. A classifier is provided, as well as a whole slide image metric for general performance evaluation of detectors. An original ensemble strategy for convolutional neural networks has been developed and its relevance in MECA-79 and general immunostaining classification tasks is discussed.

Background: Key structures for the pathophysiology of primary headache disorders such as migraine, cluster headache, and other trigeminal autonomic cephalalgias were identified by imaging in the past years. Objective: Available data on functional imaging in primary headache disorders are summarized in this review. Material and Methods: We performed a MEDLINE search on December 27th, 2020 using the search terms “primary headache” AND “imaging” that returned 453 results in English, out of which 137 were labeled reviews. All articles were evaluated for content and relevance for this narrative review. Results: The structure depicted most consistently using functional imaging in different states of primary headaches (without and with pain) was the posterior hypothalamus. Whole-brain imaging techniques such as resting-state functional resonance imaging showed a wide-ranging association of cortical and subcortical areas with human nociceptive processing in the pathophysiological mechanisms underlying the different TACs. Similarities of distinct groups of primary headache disorders, as well as their differences in brain activation across these disorders, were highlighted. Conclusion: The importance of neuroimaging research from clinical practice point of view remains the reliable and objective distinction of each individual pain syndrome from one another. This will help to make the correct clinical diagnosis and pave the way for better and effective treatment in the future. More research will be necessary to fulfill this unmet need.

Background and study aims The full-thickness resection device (FTRD) represents a novel endoscopic treatment method for lesions unresectable with conventional endoscopic techniques. The overall aim of this study was to evaluate technical success and in toto resection rates, recurrence rates, as well as immediate or late complications in patients who underwent polyp removal with the FTRD. Patients and methods Data from a prospectively collected database of 12 patients who underwent 13 over-the-scope clip-based full-thickness resections between June 2015 and June 2017 were analyzed. Follow-up endoscopy was performed in 11 out of 12 patients. Results 13 full-thickness resections were performed in 7 males and 5 females (mean age 64.3 ± 6.3 years). Mean size of the lesions removed with FTRD was 17 ± 4 mm. Location was rectum (n = 6), cecum (n = 2), ascending colon (n = 2), left flexure (n = 1) and right flexure (n = 2). Mean procedure time was 68 ± 35 minutes and mean hospital stay was 2.5 ± 1.2 days. 2 patients developed post-polypectomy syndrome, which resolved after conservative treatment. No perforations and no immediate surgical revision were needed. Histology of the 13 lesions removed with FTRD showed 5 adenomas with low grade intraepithelial neoplasia (IEN), 4 high grade IEN, 1 fibrosis, 1 fibrosis without dysplasia and 2 adenocarcinomas. Technical success was achieved in all procedures (13/13, 100 %). R0 resection was achieved in 10/12 patients (83.3 %). 2 patients underwent surgery because of recurrence or not evaluable margins. In 1 patient no residual malignancy was proven in histological examination, in the other patient residual low grade IEN adenoma. Conclusion FTRD is a minimally invasive approach with good success rate of complete resection and minimal side effects.

Hintergrund: Eine Akkumulation von eosinophilen Granulozyten (EG) am Gastrointestinaltrakt (GIT) kann aus verschiedenen pathogenetischen Ursachen erfolgen (Allergie, Autoimmunitat, idiopathische eosinophile Gastroenteritis, Neoplasie, Parasitose, Vaskulitis etc). Die eosinophile Infiltration kann von der Speiserohre bis zum Rektum jeden Organabschnitt isoliert oder kontinuierlich betreffen. Die eosinophile Osophagitis (Eo E) wurde in den letzten beiden Jahrzehnten wesentlich haufiger diagnostiziert und stellt eine wichtige Differenzialdiagnose von Patienten mit Dysphagie, refluxartigen Beschwerden, Motilitatsstorungen oder bei Thorax- und Abdominalschmerzen dar. Methodik: Die zur Diagnostik der Eo E benutzten Kriterien wurden aus dem Interdisziplinaren Datenregister fur chronisch entzundliche und allergische Magen-Darm-Erkrankungen der Universitat Erlangen analysiert extrahiert und mit einer selektiven Literaturrecherche zum Zeitpunkt Dezember 2012 zusammengefasst. Ergebnisse und Schlussfolgerung: Die Diagnostik der Eo E verlangt bei der Anamnese (z. B. veranderte Nahrungsaufnahme, Schluckstorungen, Thoraxdruck, allergische Vorerkrankungen) und bei der Endoskopie hochste Aufmerksamkeit, denn nicht selten finden sich nur diskrete Hinweise oder Auffalligkeiten der Osophagusmukosa. Typische Zeichen sind Bolusobstruktion bei jungen Mannern, erhohte Verletzbarkeit der Schleimhaut oder Ringbildungen. Die Eo E zeigt in nur ca. einem Drittel aller Falle typische endoskopische Zeichen (weise Papeln, Ring- oder Langsfurchen, Strikturen), ein Drittel zeigt verdachtige Befunde (Odem, Kontaktvulnerabilitat, blasse Mukosa) und ein Drittel ist endoskopisch unauffallig. Die endoskopische Diagnostik muss obligat histologisch durch Stufenbiopsien aus dem Osophagus erganzt werden. Die Diagnose ist gesichert, wenn mehr als 15 – 20 Eosinophile pro hochauflosendes Blickfeld (HPF) im proximalen und distalen Osophagus nachgewiesen werden konnen. Als fakultative Diagnostikmodalitaten gelten pH-Metrie, Manometrie, radiologischer KM-Schluck, Endosonografie und Thorax-Computertomografie, die nur bei speziellen Fragestellungen hinzugezogen werden mussen. Bei thorakalem Druckgefuhl sind kardiale Grunderkrankungen zu uberprufen. Weitere wichtige Differenzialdiagnosen sind die Refluxerkrankung, Mitbeteiligung des Osophagus bei Systemerkrankungen (Autoimmunopathie) oder eosinophile Gastro-Enterocolitiden und hypereosinophiles Syndrom.

Objective To investigate headache-related serum melatonin levels and melatonin excretion rhythmicity in patients with hypnic headache (HH). Background Strict sleep dependency of headache attacks is a pathognomonic feature of HH. Changes in melatonin levels, a marker for circadian rhythm, are assumed to play a pivotal role in the pathophysiology of HH. Methods Serum melatonin levels were acquired in nine patients with HH and nine age- and gender-matched healthy controls over a 20-hour time period (12 pm, 4 pm, 7 pm, 10 pm, time of headache, and 8 am). Results No significant changes of melatonin levels could be detected comparing HH patients and healthy controls. Melatonin excretion rhythmicity was not significantly altered in patients with HH (Mean melatonin level in ng/mL ± SD, patients vs controls at 12 pm: 21.5 ± 9.5 vs 13.6 ± 6.3 [P = .077], 4 pm: 18.4 ± 8.4 vs 14.0 ± 4.7 [P = .222], 7 pm: 19.4 ± 5.1 vs 15.1 ± 4.5 [P = .094], 10 pm: 59.5 ± 45.0 vs 29.4 ± 12.7 [P =.136], headache time: 96.9 ± 68.3 vs 49.1 ± 22.8 [P = .94], and 8 am: 31.6 ± 18.3 vs 26.7 ± 15.6 [P = .489]). Conclusion This study is not able to confirm a significant role of melatonin concentration changes in the pathophysiology of HH and vetoes that melatonin deficiency plays a major role in the pathophysiology of the disorder.

Background Training simulators have been used for decades with success; however, a standardized educational strategy for diagnostic EGD is still lacking. Objective Development of a training strategy for diagnostic upper endoscopy. Study design Prospective, randomized trial. Settings A total of 28 medical and surgical residents without endoscopic experience were enrolled. Basic skills evaluations were performed following a structured program involving theoretical lectures and a hands-on course in diagnostic EGD. Subsequently, stratified randomization to clinical plus simulator training (group 1, n=10), clinical training only (group 2, n=9), or simulator training only (group 3, n=9) was performed. Ten sessions of simulator training were conducted for groups 1 and 3 during the 4-month program. Group 2 underwent standard training in endoscopy without supplemental simulator training. The final evaluation was performed on the simulator and by observation of 3 clinical cases. Skills and procedural times were recorded by blinded and unblinded evaluators. Main Outcome Measurements Time to reach the duodenum, pylorus, or esophagus. Results All trainees demonstrated a significant reduction in procedure time during a simple manual skills test ( P P = .006, P = .042 and P = .017) in the simulator independent of the training strategy. Group 1 showed shorter times to intubate the esophagus (61 ± 26 seconds vs 85 ± 30 seconds and 95 ± 36 seconds) and the pylorus (183 ± 65 seconds vs 207 ± 61 seconds and 247 ± 66 seconds) during the clinical evaluation. Blinded assessment of EGD skills showed significantly better results for group 1 compared with group 3. Blinded and unblinded evaluations were not statistically different. Limitations Small sample size. Conclusions Structured simulator training supplementing clinical training in upper endoscopy appears to be superior to clinical training alone. Simulator training alone does not seem to be sufficient to improve endoscopic skills.

Background: Hypnic headache (HH) is a rare primary headache disorder characterized by strictly sleep-related headache attacks. Most patients are over the age of 50 and usually awake at the same time at night with dull bilateral head pain. The pathophysiology of this headache disorder is still enigmatic but association with rapid eye movement (REM) sleep and sleep-disordered breathing (SDB) has been suggested. Methods: Six patients with HH according to the current International Classification of Headache Disorders (ICHD-II) criteria (code 4.5) were investigated. Serial polysomnography (PSG) was performed in each patient for four consecutive nights. Results: A total of 22 HH attacks were recorded from all patients during PSG. Six of the monitored headache attacks arose from REM sleep; 16 attacks, however, arose from different non-REM (NREM) sleep stages. Five patients showed an increased apnoea/hypopnoea index (>5), indicating obstructive sleep apnoea (OSA) on some but not the majority of nights. Headache onset and occurrence of SDB were not temporally connected. Conclusions: This prospective study shows that the onset of HH was not associated with sleep stage. These results contradict the current belief that REM sleep and SDB play a crucial role in the pathophysiology of HH.

Background: Hypnic headache (HH) is a rare primary headache disorder that is characterized by exclusively sleep-related headache attacks. Because of its low prevalence, clinical features and therapeutic options are widely unknown or under discussion. Methods: Twenty patients with HH were examined and interviewed using a standardized questionnaire in regard to their clinical characteristics and effective treatment regimens. Data were evaluated according to current International Headache Society (IHS) diagnostic criteria. Individual treatment history and effective treatment options were compared with expected efficacy based on current literature. Results: In conflict to current IHS criteria, 15% of patients reported trigemino-autonomic symptoms. All patients showed distinct motor behavior during their headache attacks. In acute pain attacks caffeine was most effective. Lithium, topiramate, melatonin, amitriptyline and indomethacin were sometimes useful prophylactic treatment options but were often associated with side effects. Conclusions: Our results underline the need for modification of the IHS diagnostic criteria of HH to better reflect the actual clinical characteristics of this headache. Caffeine should be considered as first-line acute therapy. Prophylactic medical treatment should be carefully evaluated in regard to side effects in this aged patient population, as this seems to be a major concern of patients apart from pure pain reduction.

OBJECTIVE Peptic ulcers are the leading cause of upper gastrointestinal (GI) bleeding. The aim of this study was the evaluation of the recent clinical practice in drug therapy and endoscopic treatment of ulcer bleedings in Germany and to compare the results with the medical standard. METHODS A structured questionnaire (cross-sectional study) was sent to 1371 German hospitals that provide an emergency service for upper GI bleeding. The project was designed similar to a nationwide inquiry in France in 2001. Forty-four questions concerning the following topics were asked: hospital organisation, organisation of emergency endoscopy service, endoscopic and drug therapy of ulcer bleeding, endoscopic treatment of variceal bleeding. Return of the questionnaires was closed in August 2004. RESULTS Response rate was 675 / 1371 (49 %). Mean hospitals size was < 200 beds, 49 % (n = 325) had basic care level. 92 % provided a 24-hour endoscopy service, specialized nurses were available in 75 %. Fiberscopes were used only in 15 %. A mean of 10 +/- 12 (range: 0 - 160) bleeding cases/month were treated, 6 +/- 6 cases per month (60 %) were ulcer bleedings. Endoscopy was performed in 72 % immediately after stabilization but in all cases within 24 hours. The Forrest classification was used in 99 % whereas prognostic scores were applied only in 3 %. Forrest Ia,/Ib/IIa/IIb/IIc/III ulcers were indications for endoscopic therapy in 99 %/ 99 %/ 90 %/ 58 %/ 4 %/ 2 % respectively. Favoured initial treatment was injection (diluted epinephrine, mean volume 17 +/- 13 mL/lesion) followed by clipping. In re-bleedings, 93 % tried endoscopic treatment again. Scheduled re-endoscopy was performed in 63 %. PPI were used in 99.6 %, 85 % administered standard dose twice daily. PPI administration was changed from intravenous to oral with the end of fasting in nearly all hospitals. PPI administration schemes can be improved. Indications for Helicobacter pylori eradication followed rational principles. CONCLUSION Medical and endoscopic treatment of bleeding ulcers reached a high standard, although some therapeutic strategies leave room for improvement. Bigger hospitals tend to be closer to the medical standard.

OA gold - CA Naegel Abstract: Although vestibular migraine is a common cause of vertigo, affecting approximately 1% of the Western world’s population, it remains widely under-recognized and is under-diagnosed. Diagnostic criteria for vestibular migraine were recently published in collaboration with the International Headache Society and the Bárány-Society. Trials investigating the treatment of vestibular migraine are sparse but some are now underway. This review focuses on the treatments options available for vestibular migraine, based on the existing evidence base where available. Regarding acute treatments, there are two randomized controlled trials that provide evidence for the use of triptans (zolmitriptan and rizatriptan) for the management of vestibular migraine attacks. For prophylactic treatment, the evidence base is largely non-existent, since the only multicenter randomized placebo-controlled trial testing metoprolol versus placebo is still underway. Consequently, the treatment recommendations for the prophylactic treatment of vestibular migraine are mainly based on expert opinion and the treatments guidelines for migraine with and without aura. Keywords: Vestibular migraine, migraine with aura, vertigo, dizziness, migraine. Disclosure: Steffen Naegel has recieved support from Allergan. Mark Obermann has received scientific support and/or honoraria from Biogen Idec, Novartis, Sanofi-Aventis, Genzyme, Pfizer, Teva and Heel. He received research grants from Allergan, Electrocore, Heel and the German Ministry for Education and Research (BMBF). Manjit Matharu serves on the advisory board for Allergan, Medtronic and St Jude Medical, and has received payment for the development of educational presentations from Allergan, Merck Sharpe and Dohme Ltd, Johnson and Johnson, and Medtronic. Steffen Naegel, Manjit Matharu, Mark Obermann: article drafting, key concepts, revision and final approval of the manuscript. No funding was received in the publication of this article.

BACKGROUND: Since the first presentation of the compactEASIE in 1997, this training model has become established for nearly all interventional techniques in upper gastrointestinal endoscopy including ERCP. So far, training using double-balloon enteroscopy (DBE) for ERCP has not become established. AIMS: This paper presents a special organ preparation for the compactEASIE model which for the first time allows simulation of ERCP in patients who have had prior abdominal surgery. Two abdominal organ packages from freshly slaughtered pigs were used to create a postsurgical anatomic situation. RESULTS: A life-like training model was established for ERCP training in a postsurgical anatomic situation. A Roux-en-Y anastomosis was created such that the papilla was located around 100 cm beyond the pylorus. The duodenum was closed shortly above the pig papilla at the level of the pylorus. The papilla was successfully reached by DBE after 40 minutes. The papilla was cannulated and regular contrasting of the biliary system using fluoroscopy was achieved. Sphincterotomy, stent placement and exchange, and needle-knife sphincterotomy over a 7-Fr stent were conducted successfully. CONCLUSION: Modified organ preparations allow the simulation of and training in ERCP in postsurgical anatomic situations in training models using animal parts.

Background. The objective benefit of a training using the compact Erlangen Active Simulator for Interventional Endoscopy-simulator was demonstrated in two prospective educational trials (New York, France). The present study analysed whether endoscopic novices are able to reach a comparable level of endoscopic skills as in the above-described projects. Methods. Twenty-seven endoscopic novices (medical students, first year residents) were enrolled in this prospective, randomised trial. The compact Erlangen Active Simulator for Interventional Endoscopy-simulator with an upper GI-organ package and blood perfusion system was used as a training tool. Basic evaluation of endoscopic skills was performed after a practical and theoretical course in diagnostic upper GI endoscopy followed by a stratified randomisation according to the rating in endoscopic skills into intensive (n = 14) and control group (n = 13). The intensive group was trained 12 times every second week over 7 months in 4 endoscopic disciplines (manual skills, injection therapy, haemoclip, band ligation) by skilled endoscopist (three trainees/simulator). Assessment was performed (single steps/overall) using an analogue scale from 1 to 10 (1 = worst, 10 = optimal performance) by expert tutors. The control group was not trained. Blinded final evaluation of all participants was performed in January 2003. Results. We observed in all techniques applied a significant improvement of endoscopic skills and of the performance time in the intensive group compared to the control group (p < 0.001). The comparison with the previous projects showed that the intensively trained novices achieved comparable levels of performance to the GI fellows in the New York and France Project (at least 80% of the median score in three out of four techniques). Conclusion. Endoscopic novices acquired notable skills in interventional endoscopy in the simulator by an intensive, periodical training using the compactEASIE ® .

Recent studies from the UK give the debate about how to deal best with patients suffering from whiplash injury new impetus. Following whiplash injury, about 90% of patients complain about head and/or neck pain, as well as dizziness, sleep problems and anxiety. These symptoms are often referred to as whiplash-associated disorders. In the majority of cases, these complaints develop within a few days or weeks following the accident. However, 30–50% of patients experience prolonged symptoms for more than 6 months, with headache as the main complaint. In accordance with the bio-psycho-social model of chronic post-traumatic headache, the following treatment options have been suggested: (1) proper patient education with detailed explanation of the condition; (2) support of normal movement; (3) avoiding immobilization; (4) resumption of work; and (5) targeted physiotherapy. Based on current study data, intensified physiotherapy seems not to be superior to standard therapy with simple patient education and can therefore not be recommended considering cost–benefit aspects.

Cluster headache (CH) is a primary headache disorder and the most common trigeminal autonomic cephalalgia. Patients suffer from very severe unilateral headache attacks accompanied by ipsilateral trigeminal autonomic symptoms. Previous studies described a high burden of disease due to its impact on social life as well as an increased suicide ideation rate. The mean time to diagnosis in western industrialized countries is estimated at 4 years.Many treatment options for CH exist, but due to the rarity of the disease, controlled randomized clinical studies remain difficult to perform. This review summarizes the current knowledge about the treatment of CH including internationally accepted treatment guidelines, and an additional MEDLINE search (1 February 2015).International treatment recommendations and official guidelines give reassurance about specific pharmacotherapy options for CH, but only few of these are backed by sufficient scientific evidence. The limited therapeutic efficacy in some patients leads to the use of alternative, complementary, but also illicit drugs to better cope with the disease. Many single cases, case series and uncontrolled studies were performed with different substances in an attempt to find a better way to treat or prevent the excruciatingly painful attacks associated with CH. Large-scale, randomized controlled clinical trials are desperately needed in order to further increase the quality of patient care for this outstanding but terrifying disease.

BACKGROUND AND STUDY AIMS Hemoclip therapy is a well-established procedure in the treatment of gastrointestinal bleeding. Although new products are provided periodically by the industry, comparative investigations are lacking. We compared two different hemoclip devices in an experimental setting, assessing them using objective hemostatic parameters. MATERIALS AND METHODS We compared two disposable clip devices (Olympus HX-200L-135 (n = 40) vs. Wilson-Cook Tri-Clip (n = 40)) in an experimental setting using the compact Erlangen Active Simulator for Interventional Endoscopy (compactEASIE) training model equipped with an upper gastrointestinal-organ package for bleeding simulation. This was a randomized, prospective, controlled trial. Four investigators with different levels of endoscopic experience applied ten hemoclip devices of each type to the spurting vessels, the clips allocated using a randomized list for each investigator. The efficacy of hemostasis was determined by continuous measurement of the pressure within the afferent vessel before and after clip application and calculation of the relative reduction of vessel diameter by the clip device. The system pressure was recorded over the period from 1 minute before to 1 minute after clip application. A secondary end point was a subjective assessment of the whole clip application procedure by the endoscopist and the assisting nurse, using a visual analog scale (0 - 100, with 100 representing the best experience). RESULTS A total of 39/40 clips of each type were applied successfully. Both clip devices led to a significant increase in system pressure, representing significant relative reduction of vessel diameter (Olympus 5.4 +/- 7.5 %, p < 0.001; Cook 4.9 +/- 8.0 %, p < 0.001). Overall, there was no significant difference between the two devices ( P = 0.756). However, the investigator with the least experience in endoscopy (< 100 procedures) produced significantly inferior results compared with the other three investigators, who had performed between 2000 and 6000 procedures each ( P < 0.05). We found no evidence of a learning curve from the intra-observer results. The devices received good, but not significantly different, overall ratings by the endoscopists (Olympus 69 +/- 24 vs. Wilson-Cook 65 +/- 16) and by the assisting nurses (Olympus 77 +/- 9 vs. Wilson-Cook 70 +/- 22). CONCLUSIONS Using an established cadaveric training model, no significant difference was found between the two types of hemoclip devices with respect to their "hemostatic efficacy". However, the experience of the endoscopist appears to play a major role in successful clip application. The use of a feedback mechanism in emergency endoscopy training, using continuous intravessel pressure monitoring, may substantially enhance the efficacy of training, resulting in a similar improvement in clinical results.

In 1997 Hochberger and Neumann presented the "Erlangen Biosimulation Model" (commercialized as the "Erlangen Endo-Trainer") at various national and international meetings. The new compactEASIE is a simplified version of the original "Biosimulation Model" (Endo-Trainer) and is specially designed for easy handling. CompactEASIE is reduced in its features, focusing exclusively on flexible endoscopy training. The acceptance of training in endoscopic hemostasis is accepted by workshop participants, as evaluated by a questionnaire on both models.Eleven structured courses on endoscopic hemostasis for doctors and nurses organized by the same endoscopists from 3/1998 to 5/1999 were evaluated using one of both models. The questionnaires were filled in by 207/291 trainees (71%). The Endo-Trainer was used in 4 (n = 103) and the compactEASIE in 7 courses (n = 104). Both simulators were equipped with identical types of specially prepared pig-organ packages consisting of esophagus, stomach and duodenum, including artificial sewn-in vessels, polyps and varices. Blood perfusion was done with a roller pump connected to the sewn-in vessels and blood surrogate. All workshops were identical concerning the course structure: a 30-min theoretical introduction on ulcer bleeding was followed by 2 h of practical training in injection techniques and hemoclip application. The second part of variceal therapy consisted of a 30-min theoretical introduction prior to 2 h of practical training on sclerotherapy, band ligation and cyanoacrylate application. Finally, a questionnaire on the trainees' pre-experience and their rating of the different workshop sections was handed out to each participant.Previous endoscopic experience was comparable in both groups. The training in both simulators was highly accepted by the trainees (compactEASIE 95% excellent and good versus EASIE (Endo-Trainer) 97%) and did not show any significant difference (P = 0.493). Even in the assessment of the single techniques, no statistical difference was observed. Furthermore, the assessments of the closeness to reality and the endoscopic environment in both simulators were identical.Both simulators (Endo-Trainer, compactEASIE) are excellent educational tools for interventional endoscopy with a high level of acceptance. The easy-to-handle, "lightweight" compactEASIE is a significant, progress tool for the future.

Background Transcranial direct current stimulation (tDCS) of the primary motor cortex has been shown to modulate pain and trigeminal nociceptive processing. Methods Ten patients with classical trigeminal neuralgia (TN) were stimulated daily for 20 minutes over two weeks using anodal (1 mA) or sham tDCS over the primary motor cortex (M1) in a randomized double-blind cross-over design. Primary outcome variable was pain intensity on a verbal rating scale (VRS 0–10). VRS and attack frequency were assessed for one month before, during and after tDCS. The impact on trigeminal pain processing was assessed with pain-related evoked potentials (PREP) and the nociceptive blink reflex (nBR) following electrical stimulation on both sides of the forehead before and after tDCS. Results Anodal tDCS reduced pain intensity significantly after two weeks of treatment. The attack frequency reduction was not significant. PREP showed an increased N2 latency and decreased peak-to-peak amplitude after anodal tDCS. No severe adverse events were reported. Conclusion Anodal tDCS over two weeks ameliorates intensity of pain in TN. It may become a valuable treatment option for patients unresponsive to conventional treatment.

Background Vestibular migraine affects 1% of the general population, and 30%–50% of all migraine patients describe occasionally associated vertigo or dizziness. We aimed to identify brain regions altered in vestibular migraine in order to evaluate the connection between migraine and the vestibular system. Methods Seventeen patients with definite vestibular migraine were compared to 17 controls using magnetic resonance imaging-based voxel-based morphometry. Results We found grey matter (GM) volume reduction in the superior, inferior and middle (MT/V5) temporal gyrus as well as in the mid. cingulate, dorsolateral prefontal, insula, parietal and occipital cortex. A negative correlation of disease duration and GM volume was observed in areas associated with pain and vestibular processing. Moreover, there was a negative correlation between headache severity and prefrontal cortex volume. Conclusion Alterations identified in vestibular migraine resemble those previously described for migraine, but also extend to areas involved in multisensory vestibular control and central vestibular compensation possibly representing the pathoanatomic connection between migraine and the vestibular system.

Perforation of the gastrointestinal tract may cause various complications and may require emergency surgery, even in patients with significant comorbidities. Seventeen consecutive patients with indication for surgery due to a visible gastrointestinal perforation were treated with OTSC application. In this study, cause of perforation, estimated size, location, rate of perforation closure, outcome and complications were reported. In 11 of 17 patients (64.7 %), OTSC application resulted in permanent closure of perforations, thus avoiding surgery. All 11 successful cases had smaller perforation lengths (5.5 ± 1.9 mm, p

Clip application has been proven to be effective for endoscopic hemostasis. There are limited bench data on the efficacy of the over-the-scope clip (OTSC) for the treatment of spurting GI hemorrhage. We evaluated the hemodynamic efficacy of the OTSC in an established bleeding model.To evaluate the hemodynamic efficacy of the OTSC in an established bleeding model.Prospective experimental trial with historical comparison.We tested the OTSC prospectively in a validated bleeding model by using the compact Erlangen Active Simulator for Interventional Endoscopy equipped with an upper GI organ package. The artificial blood circulation system of the simulator was connected to an arterial pressure transducer. Two investigators with different endoscopic experience (4000 and 10,000 endoscopies performed) participated. Each investigator treated 16 bleeding sites in the simulator with the OTSC by using only suction (n = 8) and a novel retraction device to grasp tissue (n = 8). Systemic pressures were recorded 1 minute before, during, and 1 minute after clip application to objectify the effects of clipping on the vessel diameter.Mean and maximum reduction in vessel diameter.The application of the OTSC on the bleeding vessel led to a significant increase in systemic pressure (P.001) and decreased vessel diameter (P.001) independent of the endoscopic experience of the investigator. There was no difference in the decrease in vessel diameter based on the application technique (suction vs suction plus grasping). A historical comparison with our former trials demonstrated that the OTSC decreased the vessel diameter significantly more than other traditional endoclips.Small sample size.We could demonstrate the efficacy of the OTSC with increased hemodynamic efficiency compared with other endoscopic clip devices tested previously.

Headache attributable to nonvascular intracranial disorder is a basket of multiple, partly complex, and very diverse idiopathic or secondary disorders. By definition, the headache has to occur in a close temporal relationship to the intracranial disorder. Some of these headache disorders are caused by high or low cerebrospinal fluid pressure; noninfectious inflammatory diseases such as neurosarcoidosis, aseptic (noninfectious) meningitis, and lymphocytic hypophysitis; or intracranial neoplasm. Other nonvascular headaches, including hemicrania epileptica and postseizure headache, Chiari malformation type I, and the syndrome of transient headache and neurological deficits with cerebrospinal fluid lymphocytosis, are attributed to hypothalamic or pituitary hyper- or hyposecretion, intrathecal injection, or epileptic seizures. The clinical presentation of all these disorders can be diverse and often mimics the characteristics of primary headaches, which may delay the diagnosis.

Prospective evaluation of the new 0.025 in. Visiglide(®) guidewire to facilitate endoscopic retrograde cholangiopancreaticography using the Olympus V-scope.Interventional endoscopic retrograde cholangiopancreaticography was performed in 9 patients with the Olympus V-scope and the 0.025 in. Visiglide(®) guidewire (VS group), whilst 9 other patients underwent endoscopic retrograde cholangiopancreaticography with a conventional Olympus duodenoscope using 0.035 in. conventional guidewires (controls). Exchange time of accessories, X-ray time, dose and endoscopic retrograde cholangiopancreaticography examination time were investigated.The VS group showed a significantly lower exchange time of endoscopic retrograde cholangiopancreaticography accessories (9; 4-10s, p0.0001) than controls (29; 19-44s). The Visiglide(®) guidewire was complete fixable by the elevator in 35/36 instrument exchanges (97%) compared to 16/31 exchanges (52%) using conventional guidewires.Single-centre study, small patient numbers, two investigators.Endoscopic retrograde cholangiopancreaticography using the Olympus V-scope with the new 0.025 in. Visiglide(®) guidewire enables a 3-fold faster exchange of accessories due to a nearly complete fixation of the guidewire.

Endoscopic access to strictured biliodigestive anastomoses often is difficult and may require percutaneous transhepatic biliary drainage or reoperation. Push- or push-and-pull enteroscopy was used to diagnose disease and treat 24 postsurgical patients with suspected strictured biliodigestive anastomosis. Endoscopic retrograde cholangiography and biliary interventional procedures were used. Endoscopic accessibility, diagnosis of disease, therapeutic success, and complication rates were investigated at a single tertiary university gastroeneterology center. Push enteroscopy reached biliary enteroanastomoses in 5 of the 24 patients (20.8%), whereas push-and-pull enteroscopy found choledocho- or hepaticojejunostomies in 17 of the remaining 19 postsurgical patients (89.4%). In all, successful enteroscopic intervention was achieved for 21 of the 24 patients (87.5%), whereas only 3 patients had to undergo percutaneous cholangiodrainage (12.5%). Cicatricially changed biliodigestive anastomoses were found in 14 of 21 patients (66.6%) including a mucosal type stricture in 7 patients (50%), an intramural type stricture in 5 patients (35.7%), and a ductal type stricture in 2 patients (14.2%). The remaining seven patients (33.3%) were normal. Enteroscopic interventions at strictured biliodigestive anastomosis included ostium incision for 8 (57.1%) and endoprosthesis insertion for 13 (92.8%) of the 14 patients, with prompt resolution of cholestasis and cholangitis. The major complications for the 24 patients involving 68 double-balloon enteroscopy (DBE) examinations comprised 2 perforations (8.3% per patient), 1 mild peritonitis (4.1%), and 1 cholangitis (4.1%), whereas minor complications were experienced by up to 20.8% of the patients. Modern interventional enteroscopy yields a high rate of successful interventions for strictured biliodigestive anastomosis, requires ostium incision for mucosal and intramural types of strictures, and helps to reduce percutaneous approaches.

Objective Hypnic headache (HH) is a rare primary headache disorder characterized by strictly nocturnal headache attacks that mostly occur at the same time at night. The pathophysiology of this disease is poorly understood, but hypothalamic involvement was suspected as the hypothalamus represents the cerebral management center of sleep regulation and pain control. Methods Fourteen patients with HH and 14 age-matched and gender-matched healthy controls were investigated using magnetic resonance imaging–based voxel-based morphometry. Results We detected gray matter volume decrease in the posterior hypothalamus of HH patients. Additional gray matter decrease was observed in brain areas known to be associated with cerebral pain processing, including the cingulate cortex, operculum, and frontal lobe, as well as in the temporal lobe. Interpretation Our data confirm the hypothesized involvement of the posterior hypothalamus in the pathophysiology of HH and emphasize the importance of this structure for sleep regulation and pain control. ANN NEUROL 2010

Specific serotonin norepinephrine reuptake inhibitors (SNRIs) have been described as “better tolerated tricyclic antidepressants” or as “boosted” selective serotonin reuptake inhibitors (SSRIs). Venlafaxine has become a therapeutic reference treatment for major depression. Although less widely studied, indirect comparisons with another SNRI, milnacipran, suggest an equivalent efficacy. This paper discusses these indirect comparisons and the recently published first double-blind, head-to-head comparison. Venlafaxine has potency at serotonin transporters which is about 30-fold greater than that at norepinephrine transporters while milnacipran has a similar potency at each transporter. Thus, at low doses, venlafaxine acts essentially as a SSRI, with significant noradrenergic activity only occurring at higher doses. To overcome the problem of the differing profile of venlafaxine at increasing doses, the first head-to-head study compared the therapeutic effects and tolerability of the two antidepressants when flexibly titrated to the high dose of 200 mg/day. The study showed that the two SNRIs have similar efficacy and safety profiles. Both drugs produced about 42% remissions at the end of the 20-week study. The most frequent adverse events in both groups were nausea, dizziness, headache, and sweating. Certain specific differences in tolerability are discussed.

Although the recycling of excrements in integrated agriculture-aquaculture farming systems offers many advantages, the spread of diseases to man via aquatic organisms multiplying in excreta-laden water needs special attention. There is strong evidence that aquatic organisms may be more important vectors for human diseases than generally realized. However, conclusive epidemiological studies linking the use of excreta in aquaculture with human diseases are lacking.

Objective Persistent postural-perceptual dizziness (PPPD) is the most common vestibular disorder in the age group between 30 and 50 years. It is considered to be based on a multisensory maladjustment involving alterations of sensory response pattern including vestibular, visual and motion stimuli. Previous data supported a link between vestibular and pain mechanism. The aim of the study was to investigate whether other sensory inputs such as pain stimuli might be altered in terms of a more widespread central perception dysfunction in this disorder. Methods Nociceptive blink reflex was measured in 27 patients with PPPD and compared with 27 healthy, age and gender matched controls. The habituation of the R2 component of the blink reflex was evaluated as the percentage area-under-the curve (AUC) decrease in ten consecutive blocks of five averaged rectified responses. Additionally, clinical characteristics were evaluated. Results In patients with PPPD a lack of habituation was observed compared to healthy controls. Relative AUC decreased between the first and the tenth block by 19.48% in PPPD patients and by 31.63% (p = 0.035) in healthy controls. There was no correlation between clinical data (course of disease, comorbid depression, medication, trigger factors) or electrophysiological data (perception threshold, pain threshold, stimulus intensity) and habituation pattern. No trigeminal sensitization in terms of facilitation of absolute values could be detected. Conclusion Our study results supports the hypothesis of the multisensory dimension of impaired sensory processing in patients with PPPD extends beyond vestibular/visual motion stimuli and reflexive postural/oculomotor control mechanisms to other sensory inputs such as pain perception in terms of a more generalized disturbed habituation pattern.